[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"_public_publisher_byId_2beaf1ed-a4bc-4ed0-8010-7cc2d0b689de":3,"_public_publication_all{\"sortAscending\":false,\"sortField\":\"updateTime\",\"page\":0,\"size\":10,\"facet\":true,\"searchKey\":\"publisherId:2beaf1ed-a4bc-4ed0-8010-7cc2d0b689de,\"}":108},{"code":4,"data":5,"meta":18},"SUCCESS",{"id":6,"createTime":7,"updateTime":8,"relativeEntities":9,"slug":10,"properties":11,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":20,"manageAffiliations":39,"indexDatabases":54,"url":91,"thumbnailPath":18,"statistic":92,"gsStatistic":18,"type":107,"analyzePriority":18},"2beaf1ed-a4bc-4ed0-8010-7cc2d0b689de","2024-04-11T04:05:22.775+00:00","2025-11-21T09:52:17.700+00:00",[],"Acta-Neuropathologica-Communications",{"issn":12,"title":14},{"VOID":13},"2051-5960",{"EN":15},"Acta Neuropathologica Communications","PUBLISHER","PENDING",null,0,[21,27,33],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":23,"label":24,"description":26,"parentId":18,"standard":18,"scholarHubFieldId":18},"228d6ea6-4b2a-4153-bf22-36784b0cd31c",[],{"EN":25},"Neurology (clinical)",{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":29,"label":30,"description":32,"parentId":18,"standard":18,"scholarHubFieldId":18},"ad5ad660-08f0-4a35-bf79-d04b8774cd29",[],{"EN":31},"Cellular and Molecular Neuroscience",{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":35,"label":36,"description":38,"parentId":18,"standard":18,"scholarHubFieldId":18},"1e162c3b-d9db-4fe2-ae4f-d5f2251c2ce9",[],{"EN":37},"Pathology and Forensic Medicine",{},[40,47],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":42,"slug":18,"properties":43,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":46,"statistic":18},"67883518-0c98-470e-b6b0-160ab49bb03d",[],{"title":44},{"EN":45},"BMC",[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":49,"slug":18,"properties":50,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":53,"statistic":18},"c5894808-4e99-4047-bbce-594f58821845",[],{"title":51},{"EN":52},"BioMed Central Ltd.",[],[55,72],{"id":56,"indexDatabase":57,"url":69,"indexYears":18,"academicFieldIds":70,"indexDatabaseRanking":18},"867b73dc-93cd-42d8-a93b-6180dc5efe19",{"id":58,"createTime":18,"updateTime":18,"relativeEntities":59,"label":60,"description":62,"key":65,"publicationTags":66,"standard":18},"a4921856-b128-4d9f-8f1f-e80813d3bbd4",[],{"EN":61,"VI":61},"ISI\u002FSCIE - Science Citation Index Expanded",{"EN":63,"VI":64},"SCIE database","Cơ sở dữ liệu SCIE","scie",[67,68],"SCIE","ISI","https:\u002F\u002Fmjl.clarivate.com\u002Fsearch-results?issn=2051-5960",[71],"8d10567b-4ae4-42f8-b554-ff4a4364e08f",{"id":73,"indexDatabase":74,"url":84,"indexYears":85,"academicFieldIds":86,"indexDatabaseRanking":90},"716c2225-060e-4d59-8a5b-1f9f87fa9874",{"id":75,"createTime":18,"updateTime":18,"relativeEntities":76,"label":77,"description":79,"key":81,"publicationTags":82,"standard":18},"3c7051d4-eb7d-4c57-a56b-36fc74c5d1e9",[],{"EN":78,"VI":78},"Scopus - Elsevier",{"EN":78,"VI":80},"Cơ sở dữ liệu Scopus thuộc Elsevier","scopus",[83],"SCOPUS","https:\u002F\u002Fwww.scopus.com\u002Fsourceid\u002F21100367530","2013-2025",[87,88,89],"3ae494ca-72b1-4f7f-a18c-56c79894839d","df7b9ddd-7f90-4ca4-be60-d5ca303ebdfd","c75f06a2-b70a-4b9b-8c02-99f3ab012851","SCOPUS__Q1","https:\u002F\u002Flink.springer.com\u002Fjournal\u002F40478",{"impactFactor":19,"impactFactorByYear":93,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":98,"totalCitation":102,"totalCitationByYear":103,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":105,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},1,0.83,2,19,{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},5,4,3,68,{"2013":102},3.58,{"2013":106},13.6,"JOURNAL",{"meta":109,"data":111},{"total":110},"1241",[112,463,664,774,1010,1390,1619,1776,2418,2547],{"id":113,"createTime":114,"updateTime":115,"relativeEntities":116,"slug":117,"properties":118,"entityType":128,"verifyStatus":129,"verifyTime":130,"verifyNote":131,"languages":18,"translateLanguages":132,"viewCount":19,"primaryUrl":134,"fullTextUrl":18,"authors":135,"publicationType":403,"publisherRelationship":404,"citationCount":18,"citationInfo":18,"publishDate":459,"publishYear":460,"citationAnalyzeStatus":17,"lastCitationAnalyze":18,"indexDatabases":461,"openAccess":18,"references":18,"isForceReanalyzing":462},"20a161ba-c087-445c-87c7-63aeda9926e7","2023-12-29T16:39:21.432+00:00","2026-09-10T02:14:14.841+00:00",[],"A-toxic-gain-of-function-mechanism-in-C9orf72-ALS-impairs-the-autophagy-lysosome-pathway-in-neurons",{"abstract":119,"title":121,"references":124,"doi":126},{"EN":120},"Motor neurons (MNs), which are primarily affected in amyotrophic lateral sclerosis (ALS), are a specialized type of neurons that are long and non-dividing. Given their unique structure, these cells heavily rely on transport of organelles along their axons and the process of autophagy to maintain their cellular homeostasis. It has been shown that disruption of the autophagy pathway is sufficient to cause progressive neurodegeneration and defects in autophagy have been associated with various subtypes of ALS, including those caused by hexanucleotide repeat expansions in the C9orf72 gene. A more comprehensive understanding of the dysfunctional cellular mechanisms will help rationalize the design of potent and selective therapies for C9orf72-ALS. In this study, we used induced pluripotent stem cell (iPSC)-derived MNs from C9orf72-ALS patients and isogenic control lines to identify the underlying mechanisms causing dysregulations of the autophagy-lysosome pathway. Additionally, to ascertain the potential impact of C9orf72 loss-of-function on autophagic defects, we characterized the observed phenotypes in a C9orf72 knockout iPSC line (C9-KO). Despite the evident presence of dysfunctions in several aspects of the autophagy-lysosome pathway, such as disrupted lysosomal homeostasis, abnormal lysosome morphology, inhibition of autophagic flux, and accumulation of p62 in C9orf72-ALS MNs, we were surprised to find that C9orf72 loss-of-function had minimal influence on these phenotypes. Instead, we primarily observed impairment in endosome maturation as a result of C9orf72 loss-of-function. Additionally, our study shed light on the pathological mechanisms underlying C9orf72-ALS, as we detected an increased TBK1 phosphorylation at S172 in MNs derived from C9orf72 ALS patients. Our data provides further insight into the involvement of defects in the autophagy-lysosome pathway in C9orf72-ALS and strongly indicate that those defects are mainly due to the toxic gain-of-function mechanisms underlying C9orf72-ALS.",{"EN":122,"VI":123},"A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons","Cơ chế tăng chức năng gây độc trong bệnh ALS liên quan C9orf72 làm suy giảm con đường tự thực bào - lysosome ở các neuron",{"VOID":125},"Swinnen B, Robberecht W (2014) The phenotypic variability of amyotrophic lateral sclerosis. Nat Rev Neurol 10:661–670\nNeumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science (80–) 314:130–133\nTaylor JP, Brown RH, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539:197–206\nTalbot K (2011) Familial versus sporadic ALS: a false dichotomy? Brain 134:3429–3431\nRenton AE, Majounie E, Waite A, Simón-Sánchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268\nDeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256\nBurrell JR, Halliday GM, Kril JJ, Ittner LM, Götz J, Kiernan MC, Hodges JR (2016) The frontotemporal dementia-motor neuron disease continuum. Lancet 388:919–931\nAbramzon YA, Fratta P, Traynor BJ, Chia R (2020) The overlapping genetics of amyotrophic lateral sclerosis and frontotemporal dementia. Front Neurosci 14:1–10\nLomen-Hoerth C, Anderson T, Miller B (2002) The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59:1077–1079\nBreevoort S, Gibson S, Figueroa K, Bromberg M, Pulst S (2022) Expanding clinical spectrum of C9ORF72-related disorders and promising therapeutic strategies. Neurol Genet 8:e670\nHaeusler AR, Donnelly CJ, Rothstein JD (2016) The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease. Nat Rev Neurosci 17:383–395\nShi Y, Lin S, Staats KA, Li Y, Chang WH, Hung ST, Hendricks E, Linares GR, Wang Y, Son EY et al (2018) Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS\u002FFTD human induced motor neurons. Nat Med 24:313–325\nBraems E, Swinnen B, Van Den Bosch L (2020) C9orf72 loss‑of‑function: a trivial, stand‑alone or additive mechanism in C9 ALS\u002FFTD? Acta Neuropathol\nHaeusler AR, Donnelly CJ, Periz G, Simko EAJ, Shaw PG, Kim MS, Maragakis NJ, Troncoso JC, Pandey A, Sattler R et al (2014) C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature 507:195–200\nSwinnen B, Robberecht W, Van Den Bosch L (2019) RNA toxicity in non-coding repeat expansion disorders. EMBO J, 1–23\nWestergard T, McAvoy K, Russell K, Wen X, Pang Y, Morris B, Pasinelli P, Trotti D, Haeusler A (2019) Repeat-associated non-AUG translation in C9orf72- ALS\u002FFTD is driven by neuronal excitation and stress. EMBO Mol Med 11:1–14\nMori K, Weng S-M, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts M, Van Broeckhoven C et al (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD\u002FALS. Science 339:1335–1338\nFreibaum BD, Taylor JP (2017) The role of dipeptide repeats in C9ORF72-related ALS-FTD. Front Mol Neurosci 10:1–9\nBeckers J, Tharkeshwar AK, Van Damme P (2021) C9orf72 ALS-FTD: recent evidence for dysregulation of the autophagy-lysosome pathway at multiple levels pathway at multiple levels. Autophagy 00:1–17\nDane TL, Gill AL, Vieira FG, Denton KR (2023) Reduced C9orf72 expression exacerbates polyGR toxicity in patient iPSC-derived motor neurons and a Type I protein arginine methyltransferase inhibitor reduces that toxicity. Front Cell Neurosci, 1–14\nShao Q, Liang C, Chang Q, Zhang W, Yang M, Chen J (2019) C9orf72 deficiency promotes motor deficits of a C9ALS\u002FFTD mouse model in a dose- dependent manner. Acta Neuropathol Commun 7:9–11\nZhu Q, Jiang J, Gendron TF, Mcalonis-downes M, Jiang L, Taylor A, Garcia SD, Dastidar SG, Rodriguez MJ, King P, et al (2020) Reduced C9ORF72 function exacerbates gain of toxicity from ALS\u002FFTD-causing repeat expansion in C9orf72. Nat Neurosci\nDeng Z, Lim J, Wang Q, Purtell K, Wu S, Palomo GM, Tan H, Manfredi G, Zhao Y, Peng J et al (2020) ALS-FTLD-linked mutations of SQSTM1\u002Fp62 disrupt selective autophagy and NFE2L2\u002FNRF2 anti-oxidative stress pathway. Autophagy 16:917–931\nWebster CP, Smith EF, Grierson AJ, De Vos KJ (2018) C9orf72 plays a central role in Rab GTPase-dependent regulation of autophagy. Small GTPases 9:1–10\nRenton AE, Chiò A, Traynor BJ (2014) State of play in ALS genetics. Nat Neurosci 17:17–23\nWallings RL, Humble SW, Ward ME, Wade-Martins R (2019) Lysosomal dysfunction at the Centre of Parkinson’s disease and frontotemporal dementia\u002Famyotrophic lateral sclerosis. Trends Neurosci 42:899–912\nBain HDC, Davidson YS, Robinson AC, Ryan S, Rollinson S, Richardson A, Jones M, Snowden JS, Mann DMA (2019) The role of lysosomes and autophagosomes in frontotemporal lobar degeneration. Neuropathol Appl Neurobiol 244–261\nSullivan PM, Zhou X, Hu F (2017) Autophagy-lysosome dysfunction in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Lysosomes - Assoc Dis Methods to Study Their Funct\nRoot J, Merino P, Nuckols A, Johnson M, Kukar T (2021) Lysosome dysfunction as a cause of neurodegenerative diseases: lessons from frontotemporal dementia and amyotrophic lateral sclerosis. Neurobiol Dis 154:105360\nWilson DM 3rd, Cookson MR, Van Den Bosch L, Zetterberg H, Holtzman DM, Dewachter I (2023) Hallmarks of neurodegenerative diseases. Cell 186:693–714\nRuegsegger C, Saxena S (2016) Proteostasis impairment in ALS. Brain Res 1648:571–579\nHara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H et al (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441:885–889\nKomatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E et al (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–884\nFazal R, Boeynaems S, Swijsen A, De Decker M, Fumagalli L, Moisse M, Vanneste J, Guo W, Boon R, Vercruysse T, et al (2021) HDAC 6 inhibition restores TDP-43 pathology and axonal transport defects in human motor neurons with TARDBP mutations. EMBO J, pp 1–24\nFumagalli L, Young FL, Boeynaems S, De Decker M, Mehta AR, Swijsen A, Fazal R, Guo W, Moisse M, Beckers J, et al (2021) C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility. Sci Adv, 19–23\nGuo W, Naujock M, Fumagalli L, Vandoorne T, Baatsen P, Boon R, Ordovás L, Patel A, Welters M, Vanwelden T et al (2017) HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nat Commun 8:861\nPal A, Kretner B, Abo-Rady M, Glab H, Dash BP, Naumann M, Japtok J, Kreiter N, Dhingra A, Heutink P et al (2021) Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis. Life Sci Alliance 4:1–26\nAbo-Rady M, Kalmbach N, Pal A, Schludi C, Janosch A, Richter T, Freitag P, Bickle M, Kahlert AK, Petri S et al (2020) Knocking out C9ORF72 exacerbates axonal trafficking defects associated with hexanucleotide repeat expansion and reduces levels of heat shock proteins. Stem Cell Rep 14:390–405\nGuo W, Stoklund Dittlau K, Van Den Bosch L (2019) Axonal transport defects and neurodegeneration: molecular mechanisms and therapeutic implications. Semin Cell Dev Biol, 0–1\nFarfel-Becker T, Roney JC, Cheng XT, Li S, Cuddy SR, Sheng ZH (2019) Neuronal soma-derived degradative lysosomes are continuously delivered to distal axons to maintain local degradation capacity. Cell Rep 28:51-64.e4\nSelvaraj BT, Livesey MR, Zhao C, Gregory JM, James OT, Cleary EM, Chouhan AK, Gane AB, Perkins EM, Dando O, et al (2018) C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nat Commun, 9\nMaury Y, Côme J, Piskorowski RA, Salah-Mohellibi N, Chevaleyre V, Peschanski M, Martinat C, Nedelec S (2015) Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes. Nat Biotechnol 33:89–96\nVandoorne T, Veys K, Guo W, Sicart A, Vints K, Swijsen A, Moisse M, Eelen G, Gounko NV, Fumagalli L, et al (2019) Differentiation but not ALS mutations in FUS rewires motor neuron metabolism. Nat Commun\nCason SE, Mogre SS, Koslover EF, Holzbaur ELF, Cason SE, Mogre SS, Koslover EF, Erika LF (2023) Neuronal autophagy by the numbers neuronal autophagy by the numbers. Autophagy Rep 2\nGowrishankar S, Yuan P, Wu Y, Schrag M, Paradise S, Grutzendler J, De CP, Ferguson SM (2015) Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques. Proc Natl Acad Sci 112:E3699–E3708\nHao J, Wells MF, Niu G, Juan IGS, Limone F, Fukuda A, Leyton-Jaimes MF, Joseph B, Qian M, Mordes DA, et al (2021) Loss of TBK1 activity leads to TDP-43 proteinopathy through lysosomal dysfunction in human motor neurons. bioRxiv; 2021.10.11.464011\nMarwaha R, Sharma M (2017) DQ-Red BSA trafficking assay in cultured cells to assess Cargo delivery to lysosomes. Bio-Protocol 7\nHumphries WH, Payne CK (2012) Imaging lysosomal enzyme activity in live cells using self-quenched substrates. Anal Biochem 424:178–183\nFader CM, Colombo MI (2009) Autophagy and multivesicular bodies: two closely related partners. Cell Death Differ 16:70–78\nSchuck S, Gallagher CM, Walter P (2014) ER-phagy mediates selective degradation of endoplasmic reticulum independently of the core autophagy machinery. J Cell Sci 127:4078–4088\nAlmeida S, Gascon E, Tran H, Chou HJ, Gendron TF, Degroot S, Tapper AR, Sellier C, Charlet-Berguerand N, Karydas A et al (2013) Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol 126:385–399\nDafinca R, Scaber J, Ababneh N, Lalic T, Weir G, Christian H, Vowles J, Douglas AGL, Fletcher-Jones A, Browne C et al (2016) C9orf72 hexanucleotide expansions are associated with altered endoplasmic reticulum calcium homeostasis and stress granule formation in induced pluripotent stem cell-derived neurons from patients with amyotrophic lateral sclerosis and frontotemporal demen. Stem Cells 34:2063–2078\nDonnelly CJ, Zhang P-W, Pham JT, Haeusler AR, Heusler AR, Mistry NA, Vidensky S, Daley EL, Poth EM, Hoover B et al (2013) RNA toxicity from the ALS\u002FFTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 80:415–428\nLopez-gonzalez R, Lu Y, Gendron TF, Miller BL, Almeida S, Gao F, Lopez-gonzalez R, Lu Y, Gendron TF, Karydas A et al (2016) Mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons poly ( GR ) in C9ORF72-related ALS\u002FFTD compromises mitochondrial function and increases oxidative stress and DNA damage in iPSC-derived motor neurons. Neuron 92:383–391\nPeters OM, Cabrera GT, Tran H, Gendron TF, McKeon JE, Metterville J, Weiss A, Wightman N, Salameh J, Kim J et al (2015) Human C9ORF72 hexanucleotide expansion reproduces RNA foci and dipeptide repeat proteins but not neurodegeneration in BAC transgenic mice. Neuron 88:902–909\nHawrot J, Imhof S, Wainger BJ (2020) Modeling cell-autonomous motor neuron phenotypes in ALS using iPSCs. Neurobiol Dis 134:104680\nNeumann M, Kwong LK, Lee EB, Kremmer E, Flatley A, Xu Y, Forman MS, Troost D, Kretzschmar HA, Trojanowski JQ et al (2009) Phosphorylation of S409\u002F410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol 117:137–149\nBilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J et al (2012) Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proc Natl Acad Sci 109:5803–5808\nBerning BA, Walker AK (2019) The pathobiology of TDP-43 C-terminal fragments in ALS and FTLD. Front Neurosci 13:1–27\nLiu WJ, Ye L, Huang WF, Guo LJ, Xu ZG, Wu HL, Yang C, Liu HF (2016) P62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation. Cell Mol Biol Lett 21:1–14\nIchimura Y, Komatsu M (2022) Considering the mechanism by which droplets of ALS-FTD-associated SQSTM1\u002Fp62 mutants cause pathology. Autophagy Rep 1:9–13\nIchimura Y, Kumanomidou T, Sou YS, Mizushima T, Ezaki J, Ueno T, Kominami E, Yamane T, Tanaka K, Komatsu M (2008) Structural basis for sorting mechanism of p62 in selective autophagy. J Biol Chem 283:22847–22857\nMackenzie IRA, Frick P, Neumann M (2014) The neuropathology associated with repeat expansions in the C9ORF72 gene. Acta Neuropathol 127:347–357\nCooper-Knock J, Hewitt C, Highley JR, Brockington A, Milano A, Man S, Martindale J, Hartley J, Walsh T, Gelsthorpe C et al (2012) Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72. Brain 135:751–764\nRamos-Campoy O, Ávila-Polo R, Grau-Rivera O, Antonell A, Clarimón J, Rojas-García R, Charif S, Santiago-Valera V, Hernandez I, Aguilar M et al (2018) Systematic screening of ubiquitin\u002Fp62 aggregates in cerebellar cortex expands the neuropathological phenotype of the C9orf72 expansion mutation. J Neuropathol Exp Neurol 77:703–709\nAmaravadi RK, Winkler JD (2012) Lys05: a new lysosomal autophagy inhibitor. Autophagy 8:1383–1384\nBalendra R, Isaacs AM (2018) C9orf72-mediated ALS and FTD: multiple pathways to disease. Nat Rev Neurol 14:544–558\nLaflamme C, McKeever P, Kumar R, Schwartz J, Kolahdouzan M, Chen CX-Q, You Z, Benaliouad F, Gileadi O, McBride HM, et al (2019) Implementation of an antibody validation procedure: application to the major ALS\u002FFTD disease gene C9ORF72. Elife 499350\nO’Rourke JG, Bogdanik L, Yáñez A, Lall D, Wolf AJ, Muhammad AKMG, Ho R, Carmona S, Vit JP, Zarrow J, et al (2016) C9orf72 is required for proper macrophage and microglial function in mice. Science (80-) 351:1324–1329\nWebster CP, Smith EF, Bauer CS, Moller A, Hautbergue GM, Ferraiuolo L, Myszczynska MA, Higginbottom A, Walsh MJ, Whitworth AJ et al (2016) The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO J 35:1656–1676\nAoki Y, Manzano R, Lee Y, Dafinca R, Aoki M, Douglas AGL, Varela MA, Sathyaprakash C, Scaber J, Barbagallo P et al (2017) C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia. Brain 140:887–897\nSullivan PM, Zhou X, Robins AM, Paushter DH, Kim D, Smolka MB, Hu F (2016) The ALS\u002FFTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. Acta Neuropathol Commun 4:51\nFarg MA, Sundaramoorthy V, Sultana JM, Yang S, Atkinson RAK, Levina V, Halloran MA, Gleeson PA, Blair IP, Soo KY et al (2014) C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum Mol Genet 23:3579–3595\nAmick J, Roczniak-Ferguson A, Ferguson SM (2016) C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling. Mol Biol Cell 27:3040–3051\nShao W, Todd TW, Wu Y, Jones CY, Tong J, Jansen-west K, Daughrity LM, Park J, Koike Y, Kurti A, et al (2022) Two FTD-ALS genes converge on the endosomal pathway to induce TDP-43 pathology and degeneration. Science (80-) 99:94–99\nZhang C, Shang G, Gui X, Zhang X, Bai X, Chen ZJ (2019) Structural basis of STING binding with and phosphorylation by TBK1. Nature 567:394–398\nOakes JA, Davies MC, Collins MO (2017) TBK1: a new player in ALS linking autophagy and neuroinflammation. Mol Brain 10:1–10\nLiu G, Coyne AN, Pei F, Vaughan S, Chaung M, Zarnescu DC, Buchan JR (2017) Endocytosis regulates TDP-43 toxicity and turnover. Nat Commun 8\nBarmada SJ, Serio A, Arjun A, Bilican B, Daub A, Ando DM, Tsvetkov A, Pleiss M, Li X, Peisach D et al (2014) Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol 10:677–685\nOsaki T, Uzel SGM, Kamm RD (2018) Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons. Sci Adv 4:eaat5847\nEgawa N, Kitaoka S, Tsukita K, Naitoh M, Takahashi K, Yamamoto T, Adachi F, Kondo T, Okita K, Asaka I, et al (2012) Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med 4:145ra104\nKreiter N, Pal A, Lojewski X, Corcia P, Naujock M, Reinhardt P, Sterneckert J, Petri S, Wegner F, Storch A et al (2018) Age-dependent neurodegeneration and organelle transport deficiencies in mutant TDP43 patient-derived neurons are independent of TDP43 aggregation. Neurobiol Dis 115:167–181\nFujimori K, Ishikawa M, Otomo A, Atsuta N, Nakamura R, Akiyama T, Hadano S, Aoki M, Saya H, Sobue G et al (2018) Modeling sporadic ALS in iPSC-derived motor neurons identifies a potential therapeutic agent. Nat Med 24:1579–1589\nÖzkan N, Koppers M, van Soest I, van Harten A, Jurriens D, Liv N, Klumperman J, Kapitein LC, Hoogenraad CC, Farías GG (2021) ER–lysosome contacts at a pre-axonal region regulate axonal lysosome availability. Nat Commun 12:1–18\nHenry AG, Aghamohammadzadeh S, Samaroo H, Chen Y, Mou K, Needle E, Hirst WD (2015) Pathogenic LRRK2 mutations, through increased kinase activity, produce enlarged lysosomes with reduced degradative capacity and increase ATP13A2 expression. Hum Mol Genet 24:6013–6028\nBurkhardt MF, Martinez FJ, Wright S, Ramos C, Volfson D, Mason M, Garnes J, Dang V, Lievers J, Shoukat-Mumtaz U et al (2013) A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells. Mol Cell Neurosci 56:355–364\nWorkman MJ, Lim RG, Wu J, Frank A, Ornelas L, Panther L, Galvez E, Perez D, Meepe I, Lei S, et al (2023) Large-scale differentiation of iPSC-derived motor neurons from ALS and control subjects. Neuron, 1–14\nMasrori P, Bijnens B, Davie K, Kumar Poovathingal S, Storm A, Hersmus N, Fumagalli L, Van Den Bosch L, Fiers M, Thal R, et al (2022) Hexanucleotide repeat expansions in C9orf72 alter microglial responses and prevent a coordinated glial reaction in ALS. bioRxiv 2022\nBanerjee P, Mehta AR, Nirujogi RS, Cooper J, Nanda J, Longden J, Burr K, Salzinger A, Newton J, Story D, et al (2023) Cell-autonomous immune dysfunction driven by disrupted autophagy in C9orf72 -ALS iPSC-derived microglia contributes to neurodegeneration. Sci Adv 2022.05.12.491675\nHess MW, Huber LA (2021) Measuring lysosomal size and frequency by electron microscopy. Methods Cell Biol 164:47–61\nRijal Upadhaya A, Capetillo-Zarate E, Kosterin I, Abramowski D, Kumar S, Yamaguchi H, Walter J, Fändrich M, Staufenbiel M, Thal DR (2012) Dispersible amyloid β-protein oligomers, protofibrils, and fibrils represent diffusible but not soluble aggregates: their role in neurodegeneration in amyloid precursor protein (APP) transgenic mice. Neurobiol Aging 33:2641–2660\nTinevez JY, Perry N, Schindelin J, Hoopes GM, Reynolds GD, Laplantine E, Bednarek SY, Shorte SL, Eliceiri KW (2017) TrackMate: an open and extensible platform for single-particle tracking. Methods 115:80–90\nBrooks BR, Miller RG, Swash M, Munsat TL (2000) El escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 1:293–299\nde Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto H, Nodera H, Shefner J et al (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119:497–503\nDe Carvalho M, Swash M (2009) Awaji diagnostic algorithm increases sensitivity of El Escorial criteria for ALS diagnosis. Amyotroph Lateral Scler 10:53–57\nGorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF et al (2011) Classification of primary progressive aphasia and its variants. Neurology 76:1006–1014\nRascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, Van Swieten JC, Seelaar H, Dopper EGP, Onyike CU et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477",{"VOID":127},"10.1186\u002Fs40478-023-01648-0","PUBLICATION","VERIFIED","2024-12-13T05:32:26.427+00:00","Auto Verify",[133],"VI","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-023-01648-0",[136,161,190,214,234,263,283,306,331,352,373],{"id":137,"sortIndex":19,"researcher":18,"roles":138,"affiliations":140,"properties":158,"displayName":160,"givenName":18,"familyName":18},"3baeb484-f8b8-43f7-8ccb-f86b727adece",[139],"AUTHOR",[141,149],{"id":142,"sortIndex":19,"affiliation":143,"properties":18},"dafb927a-92ea-4d30-a5ef-33a8ed51ed52",{"id":142,"createTime":18,"updateTime":18,"relativeEntities":144,"slug":18,"properties":145,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":148,"statistic":18},[],{"title":146},{"VI":147},"Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), KU Louvain – University of Leuven, Leuven, Belgium",[],{"id":150,"sortIndex":94,"affiliation":151,"properties":157},"ca41d359-ad0f-4c8a-8b50-037f565e9fdd",{"id":150,"createTime":18,"updateTime":18,"relativeEntities":152,"slug":18,"properties":153,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":156,"statistic":18},[],{"title":154},{"VI":155},"Center for Brain and Disease Research, Laboratory of Neurobiology, VIB, Leuven, Belgium",[],{},{"title":159},{"VI":160},"Jimmy Beckers",{"id":162,"sortIndex":94,"researcher":18,"roles":163,"affiliations":164,"properties":187,"displayName":189,"givenName":18,"familyName":18},"d23507ae-f768-4fd6-b865-e7a39189ffd9",[139],[165,171,178],{"id":142,"sortIndex":19,"affiliation":166,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":167,"slug":18,"properties":168,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":170,"statistic":18},[],{"title":169},{"VI":147},[],{"id":150,"sortIndex":94,"affiliation":172,"properties":177},{"id":150,"createTime":18,"updateTime":18,"relativeEntities":173,"slug":18,"properties":174,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":176,"statistic":18},[],{"title":175},{"VI":155},[],{},{"id":179,"sortIndex":96,"affiliation":180,"properties":186},"babbbb3c-4caa-4943-985e-c19687214267",{"id":179,"createTime":18,"updateTime":18,"relativeEntities":181,"slug":18,"properties":182,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":185,"statistic":18},[],{"title":183},{"VI":184},"Department of Human Genetics, KU Leuven, Louvain, Belgium",[],{},{"title":188},{"VI":189},"Arun Kumar Tharkeshwar",{"id":191,"sortIndex":96,"researcher":18,"roles":192,"affiliations":193,"properties":211,"displayName":213,"givenName":18,"familyName":18},"53adf717-4d9a-4134-a590-46567cb6727f",[139],[194,202],{"id":195,"sortIndex":19,"affiliation":196,"properties":18},"0285df34-d97b-423b-8554-1c1ee5fb5b40",{"id":195,"createTime":18,"updateTime":18,"relativeEntities":197,"slug":18,"properties":198,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":201,"statistic":18},[],{"title":199},{"VI":200},"Center for Molecular Neurology, Microglia and Inflammation in Neurological Disorders (MIND) Lab, VIB, Antwerp, Belgium",[],{"id":203,"sortIndex":94,"affiliation":204,"properties":210},"21ea883b-784a-40d9-acc3-ae077e1a3638",{"id":203,"createTime":18,"updateTime":18,"relativeEntities":205,"slug":18,"properties":206,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":209,"statistic":18},[],{"title":207},{"VI":208},"Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium",[],{},{"title":212},{"VI":213},"Laura Fumagalli",{"id":215,"sortIndex":101,"researcher":18,"roles":216,"affiliations":217,"properties":231,"displayName":233,"givenName":18,"familyName":18},"28eb17e5-0b75-4a3d-825b-97cbef3e1ef1",[139],[218,224],{"id":142,"sortIndex":19,"affiliation":219,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":220,"slug":18,"properties":221,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":223,"statistic":18},[],{"title":222},{"VI":147},[],{"id":150,"sortIndex":94,"affiliation":225,"properties":230},{"id":150,"createTime":18,"updateTime":18,"relativeEntities":226,"slug":18,"properties":227,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":229,"statistic":18},[],{"title":228},{"VI":155},[],{},{"title":232},{"VI":233},"Matilde Contardo",{"id":235,"sortIndex":100,"researcher":18,"roles":236,"affiliations":237,"properties":260,"displayName":262,"givenName":18,"familyName":18},"83a90c48-ae1b-462d-80a1-ec5d30571de2",[139],[238,244,251],{"id":142,"sortIndex":19,"affiliation":239,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":240,"slug":18,"properties":241,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":243,"statistic":18},[],{"title":242},{"VI":147},[],{"id":150,"sortIndex":94,"affiliation":245,"properties":250},{"id":150,"createTime":18,"updateTime":18,"relativeEntities":246,"slug":18,"properties":247,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":249,"statistic":18},[],{"title":248},{"VI":155},[],{},{"id":252,"sortIndex":96,"affiliation":253,"properties":259},"e71fa943-5862-4568-be24-c8ac71274410",{"id":252,"createTime":18,"updateTime":18,"relativeEntities":254,"slug":18,"properties":255,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":258,"statistic":18},[],{"title":256},{"VI":257},"Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), KU Louvain – University of Leuven, Leuven, Belgium",[],{},{"title":261},{"VI":262},"Evelien Van Schoor",{"id":264,"sortIndex":99,"researcher":18,"roles":265,"affiliations":266,"properties":280,"displayName":282,"givenName":18,"familyName":18},"7c2ce230-4b59-4c40-af07-6fe08bd958ed",[139],[267,273],{"id":142,"sortIndex":19,"affiliation":268,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":269,"slug":18,"properties":270,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":272,"statistic":18},[],{"title":271},{"VI":147},[],{"id":150,"sortIndex":94,"affiliation":274,"properties":279},{"id":150,"createTime":18,"updateTime":18,"relativeEntities":275,"slug":18,"properties":276,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":278,"statistic":18},[],{"title":277},{"VI":155},[],{},{"title":281},{"VI":282},"Raheem Fazal",{"id":284,"sortIndex":285,"researcher":18,"roles":286,"affiliations":287,"properties":303,"displayName":305,"givenName":18,"familyName":18},"8738df1a-608b-429b-b372-d867acad395a",6,[139],[288,294],{"id":252,"sortIndex":19,"affiliation":289,"properties":18},{"id":252,"createTime":18,"updateTime":18,"relativeEntities":290,"slug":18,"properties":291,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":293,"statistic":18},[],{"title":292},{"VI":257},[],{"id":295,"sortIndex":94,"affiliation":296,"properties":302},"8cffcc3d-11df-42ed-b912-100e6b19f3a7",{"id":295,"createTime":18,"updateTime":18,"relativeEntities":297,"slug":18,"properties":298,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":301,"statistic":18},[],{"title":299},{"VI":300},"Department of Pathology, University Hospitals Leuven, Louvain, Belgium",[],{},{"title":304},{"VI":305},"Dietmar Rudolf Thal",{"id":307,"sortIndex":308,"researcher":18,"roles":309,"affiliations":310,"properties":328,"displayName":330,"givenName":18,"familyName":18},"6d2c98c7-5bcd-43f0-bb3a-73b75985652d",7,[139],[311,319],{"id":312,"sortIndex":19,"affiliation":313,"properties":18},"2941838a-3649-4c44-af95-4488165f4455",{"id":312,"createTime":18,"updateTime":18,"relativeEntities":314,"slug":18,"properties":315,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":318,"statistic":18},[],{"title":316},{"EN":317},"UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK",[],{"id":320,"sortIndex":94,"affiliation":321,"properties":327},"b36f9f6b-42e5-4f67-83ea-bda03542b179",{"id":320,"createTime":18,"updateTime":18,"relativeEntities":322,"slug":18,"properties":323,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":326,"statistic":18},[],{"title":324},{"VI":325},"Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK",[],{},{"title":329},{"VI":330},"Siddharthan Chandran",{"id":332,"sortIndex":333,"researcher":18,"roles":334,"affiliations":335,"properties":349,"displayName":351,"givenName":18,"familyName":18},"045a04c3-8b5e-4070-acdd-1f3a8b16f154",8,[139],[336,342],{"id":195,"sortIndex":19,"affiliation":337,"properties":18},{"id":195,"createTime":18,"updateTime":18,"relativeEntities":338,"slug":18,"properties":339,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":341,"statistic":18},[],{"title":340},{"VI":200},[],{"id":203,"sortIndex":94,"affiliation":343,"properties":348},{"id":203,"createTime":18,"updateTime":18,"relativeEntities":344,"slug":18,"properties":345,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":347,"statistic":18},[],{"title":346},{"VI":208},[],{},{"title":350},{"VI":351},"Renzo Mancuso",{"id":353,"sortIndex":354,"researcher":18,"roles":355,"affiliations":356,"properties":370,"displayName":372,"givenName":18,"familyName":18},"71fba74e-b428-4592-8513-d7fda988ec50",9,[139],[357,363],{"id":142,"sortIndex":19,"affiliation":358,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":359,"slug":18,"properties":360,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":362,"statistic":18},[],{"title":361},{"VI":147},[],{"id":150,"sortIndex":94,"affiliation":364,"properties":369},{"id":150,"createTime":18,"updateTime":18,"relativeEntities":365,"slug":18,"properties":366,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":368,"statistic":18},[],{"title":367},{"VI":155},[],{},{"title":371},{"VI":372},"Ludo Van Den Bosch",{"id":374,"sortIndex":375,"researcher":18,"roles":376,"affiliations":377,"properties":400,"displayName":402,"givenName":18,"familyName":18},"1fafe98c-6197-42ce-b15a-230da3c5db86",10,[139],[378,384,391],{"id":142,"sortIndex":19,"affiliation":379,"properties":18},{"id":142,"createTime":18,"updateTime":18,"relativeEntities":380,"slug":18,"properties":381,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":383,"statistic":18},[],{"title":382},{"VI":147},[],{"id":150,"sortIndex":94,"affiliation":385,"properties":390},{"id":150,"createTime":18,"updateTime":18,"relativeEntities":386,"slug":18,"properties":387,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":389,"statistic":18},[],{"title":388},{"VI":155},[],{},{"id":392,"sortIndex":96,"affiliation":393,"properties":399},"44039bf0-d1ae-4ed3-a2a7-545a21cf1a26",{"id":392,"createTime":18,"updateTime":18,"relativeEntities":394,"slug":18,"properties":395,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":398,"statistic":18},[],{"title":396},{"VI":397},"Department of Neurology, University Hospitals Leuven, Louvain, Belgium",[],{},{"title":401},{"VI":402},"Philip Van Damme","ARTICLE",{"url":134,"publisher":405,"properties":454},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":406,"slug":10,"properties":407,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":410,"manageAffiliations":423,"indexDatabases":434,"url":91,"thumbnailPath":18,"statistic":449,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":408,"title":409},{"VOID":13},{"EN":15},[411,415,419],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":412,"label":413,"description":414,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":416,"label":417,"description":418,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":420,"label":421,"description":422,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[424,429],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":425,"slug":18,"properties":426,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":428,"statistic":18},[],{"title":427},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":430,"slug":18,"properties":431,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":433,"statistic":18},[],{"title":432},{"EN":52},[],[435,442],{"id":56,"indexDatabase":436,"url":69,"indexYears":18,"academicFieldIds":441,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":437,"label":438,"description":439,"key":65,"publicationTags":440,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":443,"url":84,"indexYears":85,"academicFieldIds":448,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":444,"label":445,"description":446,"key":81,"publicationTags":447,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":450,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":451,"totalCitation":102,"totalCitationByYear":452,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":453,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":455,"volume":457},{"VOID":456},"1-22",{"VOID":458},"11","2023-09-18",2023,[67,90],false,{"id":464,"createTime":465,"updateTime":466,"relativeEntities":467,"slug":468,"properties":469,"entityType":128,"verifyStatus":129,"verifyTime":480,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":481,"fullTextUrl":18,"authors":482,"publicationType":403,"publisherRelationship":601,"citationCount":656,"citationInfo":657,"publishDate":660,"publishYear":658,"citationAnalyzeStatus":661,"lastCitationAnalyze":662,"indexDatabases":663,"openAccess":18,"references":18,"isForceReanalyzing":462},"3d32bfd5-fd40-4538-80bd-73df4fda1eb7","2024-01-24T14:16:37.013+00:00","2026-07-27T03:29:17.181+00:00",[],"Global-activation-of-oncogenic-pathways-underlies-therapy-resistance-in-diffuse-midline-glioma",{"abstract":470,"title":472,"gsPaper":474,"references":476,"doi":478},{"EN":471},"Diffuse midline gliomas (DMGs) are aggressive pediatric brain tumors with dismal prognosis due to therapy-resistant tumor growth and invasion. We performed the first integrated histologic\u002Fgenomic\u002Fproteomic analysis of 21 foci from three pontine DMG cases with supratentorial dissemination. Histone H3.3-K27M was the driver mutation, usually at high variant allele fraction due to recurrent chromosome 1q copy number gain, in combination with germline variants in ATM, FANCM and MYCN genes. Both previously reported and novel recurrent copy number variations and somatic pathogenic mutations in chromatin remodeling, DNA damage response and PI3K\u002FMAPK growth pathways were variably detected, either in multiple or isolated foci. Proteomic analysis showed global upregulation of histone H3, lack of H3-K27 trimethylation, and further impairment of polycomb repressive complex 2 by ASXL1 downregulation. Activation of oncogenic pathways resulted from combined upregulation of N-MYC, SOX2, p65\u002Fp50 NF-κB and STAT3 transcription factors, EGFR, FGFR2, PDGFRα\u002Fβ receptor tyrosine kinases, and downregulation of PHLPP1\u002F2, PTEN and p16\u002FINK4A tumor suppressors. Upregulation of SMAD4, PAI-1, CD44, and c-SRC in multiple foci most likely contributed to invasiveness. This integrated comprehensive analysis revealed a complex spatiotemporal evolution in diffuse intrisic pontine glioma, recommending pontine and cerebellar biopsies for accurate populational genetic characterization, and delineated common signaling pathways and potential therapeutic targets. It also revealed an unsuspected activation of a multitude of oncogenic pathways, including cancer cell reprogramming, explaining the resistance of DMG to current therapies.",{"EN":473},"Global activation of oncogenic pathways underlies therapy resistance in diffuse midline glioma",{"VOID":475},"[\"17682261858204152165\"]",{"VOID":477},"Louis DN, Ohgaki H, Wiestler OD, Caveneee WK (2016) WHO classification of Tumors of the central nervous system. IARC, Lyon\nChiang JC, Ellison DW (2017) Molecular pathology of paediatric central nervous system tumours. J Pathol 241:159–172\nBenitez-Ribas D, Cabezon R, Florez-Grau G, Molero MC, Puerta P, Guillen A et al (2018) Immune response generated with the Administration of Autologous Dendritic Cells Pulsed with an Allogenic Tumoral cell-lines lysate in patients with newly diagnosed diffuse intrinsic Pontine Glioma. Front Oncol 8:127\nChheda ZS, Kohanbash G, Okada K, Jahan N, Sidney J, Pecoraro M et al (2018) Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy. J Exp Med 215:141–157\nMathew RK, Rutka JT (2018) Diffuse intrinsic Pontine Glioma : clinical features, molecular genetics, and novel targeted therapeutics. J Korean Neurosurg Soc 61:343–351\nWilliams MJ, Singleton WG, Lowis SP, Malik K, Kurian KM (2017) Therapeutic targeting of histone modifications in adult and Pediatric high-grade Glioma. Front Oncol 7:45\nSchwartzentruber J, Korshunov A, Liu XY, Jones DT, Pfaff E, Jacob K et al (2012) Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature 482:226–231\nWu G, Broniscer A, McEachron TA, Lu C, Paugh BS, Becksfort J et al (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253\nKhuong-Quang DA, Buczkowicz P, Rakopoulos P, Liu XY, Fontebasso AM, Bouffet E et al (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124:439–447\nHoffman LM, Veldhuijzen van Zanten SEM, Colditz N, Baugh J, Chaney B, Hoffmann M et al (2018) Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic Pontine Glioma (DIPG): a collaborative report from the international and European Society for Pediatric Oncology DIPG registries. J Clin Oncol 36:1963–1972\nBuczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M et al (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46:451–456\nCastel D, Philippe C, Calmon R, Le Dret L, Truffaux N, Boddaert N et al (2015) Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol 130:815–827\nHoffman LM, DeWire M, Ryall S, Buczkowicz P, Leach J, Miles L et al (2016) Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics. Acta Neuropathol Commun 4:1\nKoschmann C, Zamler D, MacKay A, Robinson D, Wu YM, Doherty R et al (2016) Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma. Oncotarget 7:65696–65706\nPaugh BS, Broniscer A, Qu C, Miller CP, Zhang J, Tatevossian RG et al (2011) Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29:3999–4006\nPaugh BS, Zhu X, Qu C, Endersby R, Diaz AK, Zhang J et al (2013) Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res 73:6219–6229\nNikbakht H, Panditharatna E, Mikael LG, Li R, Gayden T, Osmond M et al (2016) Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma. Nat Commun 7:11185\nGeorgescu MM, Pinho Mda C, Richardson TE, Torrealba J, Buja LM, Milewicz DM et al (2015) The defining pathology of the new clinical and histopathologic entity ACTA2-related cerebrovascular disease. Acta Neuropathol Commun 3:81\nDekaban AS (1978) Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 4:345–356\nGeorgescu MM, Olar A, Mobley BC, Faust PL, Raisanen JM (2018) Epithelial differentiation with microlumen formation in meningioma: diagnostic utility of NHERF1\u002FEBP50 immunohistochemistry. Oncotarget 9:28652–28665\nGeorgescu MM, Yell P, Mobley BC, Shang P, Georgescu T, Wang SH et al (2015) NHERF1\u002FEBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma. Acta Neuropathol Commun 3:11\nGeorgescu MM, Li Y, Islam MZ, Notarianni C, Sun H, Olar A et al (2019) Mutations of the MAPK\u002FTSC\u002FmTOR pathway characterize periventricular glioblastoma with epithelioid SEGA-like morphology-morphological and therapeutic implications. Oncotarget 10:4038–4052\nGeorgescu MM, Nanda A, Li Y, Mobley BC, Faust PL, Raisanen JM et al (2020) Mutation status and epithelial differentiation stratify recurrence risk in Chordoid meningioma-a Multicenter study with high prognostic relevance. Cancers (Basel) 12:225\nGeorgescu MM, Olar A (2020) Genetic and histologic spatiotemporal evolution of recurrent, multifocal, multicentric and metastatic glioblastoma. Acta Neuropathol Commun 8:10\nBeaubier N, Bontrager M, Huether R, Igartua C, Lau D, Tell R et al (2019) Integrated genomic profiling expands clinical options for patients with cancer. Nat Biotechnol 37:1351–1360\nAgarwal NK, Zhu X, Gagea M, White CL 3rd, Cote G, Georgescu MM (2014) PHLPP2 suppresses the NF-kappaB pathway by inactivating IKKbeta kinase. Oncotarget 5:815–823\nMolina JR, Agarwal NK, Morales FC, Hayashi Y, Aldape KD, Cote G et al (2012) PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. Oncogene 31:1264–1274\nZhu X, Morales FC, Agarwal NK, Dogruluk T, Gagea M, Georgescu MM (2013) Moesin is a glioma progression marker that induces proliferation and Wnt\u002Fbeta-catenin pathway activation via interaction with CD44. Cancer Res 73:1142–1155\nSolomon DA, Wood MD, Tihan T, Bollen AW, Gupta N, Phillips JJ et al (2016) Diffuse midline Gliomas with histone H3-K27M mutation: a series of 47 cases assessing the Spectrum of morphologic variation and associated genetic alterations. Brain Pathol 26:569–580\nHagiwara T, Nakaya K, Nakamura Y, Nakajima H, Nishimura S, Taya Y (1992) Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II. Eur J Biochem 209:945–950\nKiiski JI, Pelttari LM, Khan S, Freysteinsdottir ES, Reynisdottir I, Hart SN et al (2014) Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer. Proc Natl Acad Sci U S A 111:15172–15177\nKatoh M (2013) Functional and cancer genomics of ASXL family members. Br J Cancer 109:299–306\nMackay A, Burford A, Carvalho D, Izquierdo E, Fazal-Salom J, Taylor KR et al (2017) Integrated molecular meta-analysis of 1,000 Pediatric high-grade and diffuse intrinsic Pontine Glioma. Cancer Cell 32:520–37.e5\nAstolfi A, Fiore M, Melchionda F, Indio V, Bertuccio SN, Pession A (2019) BCOR involvement in cancer. Epigenomics 11:835–855\nLee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D et al (2007) Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318:447–450\nShreeram S, Demidov ON, Hee WK, Yamaguchi H, Onishi N, Kek C et al (2006) Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol Cell 23:757–764\nWu G, Diaz AK, Paugh BS, Rankin SL, Ju B, Li Y et al (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46:444–450\nZhang L, Chen LH, Wan H, Yang R, Wang Z, Feng J et al (2014) Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas. Nat Genet 46:726–730\nZehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR et al (2017) Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 23:703–713\nLabreche K, Simeonova I, Kamoun A, Gleize V, Chubb D, Letouze E et al (2015) TCF12 is mutated in anaplastic oligodendroglioma. Nat Commun 6:7207\nKovaleva V, Geissler AL, Lutz L, Fritsch R, Makowiec F, Wiesemann S et al (2016) Spatio-temporal mutation profiles of case-matched colorectal carcinomas and their metastases reveal unique de novo mutations in metachronous lung metastases by targeted next generation sequencing. Mol Cancer 15:63\nUrick ME, Rudd ML, Godwin AK, Sgroi D, Merino M, Bell DW (2011) PIK3R1 (p85alpha) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res 71:4061–4067\nUpadhyaya M, Maynard J, Osborn M, Harper PS (1997) Six novel mutations in the neurofibromatosis type 1 (NF1) gene. Hum Mutat 10:248–250\nWei X, Walia V, Lin JC, Teer JK, Prickett TD, Gartner J et al (2011) Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nat Genet 43:442–446\nJones C, Baker SJ (2014) Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat Rev Cancer 14. 651-61\nKumar S, Lu B, Dixit U, Hossain S, Liu Y, Li J et al (2015) Reciprocal regulation of Abl kinase by Crk Y251 and Abi1 controls invasive phenotypes in glioblastoma. Oncotarget 6:37792–37807\nTakino T, Nakada M, Miyamori H, Yamashita J, Yamada KM, Sato H (2003) CrkI adapter protein modulates cell migration and invasion in glioblastoma. Cancer Res 63:2335–2337\nZhang YK, Qu YY, Lin Y, Wu XH, Chen HZ, Wang X et al (2017) Enoyl-CoA hydratase-1 regulates mTOR signaling and apoptosis by sensing nutrients. Nat Commun 8:464\nZarghooni M, Bartels U, Lee E, Buczkowicz P, Morrison A, Huang A et al (2010) Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28:1337–1344\nBurma S, Chen BP, Murphy M, Kurimasa A, Chen DJ (2001) ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 276:42462–42467\nZambetti GP, Levine AJ (1993) A comparison of the biological activities of wild-type and mutant p53. FASEB J 7:855–865\nGraham V, Khudyakov J, Ellis P, Pevny L (2003) SOX2 functions to maintain neural progenitor identity. Neuron 39:749–765\nHua X, Miller ZA, Wu G, Shi Y, Lodish HF (1999) Specificity in transforming growth factor beta-induced transcription of the plasminogen activator inhibitor-1 gene: interactions of promoter DNA, transcription factor muE3, and Smad proteins. Proc Natl Acad Sci U S A 96:13130–13135\nHjelmeland MD, Hjelmeland AB, Sathornsumetee S, Reese ED, Herbstreith MH, Laping NJ et al (2004) SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility. Mol Cancer Ther 3:737–745\nHjortland GO, Bjornland K, Pettersen S, Garman-Vik SS, Emilsen E, Nesland JM et al (2003) Modulation of glioma cell invasion and motility by adenoviral gene transfer of PAI-1. Clin Exp Metastasis 20:301–309\nBourguignon LY, Zhu H, Shao L, Chen YW (2001) CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. J Biol Chem 276:7327–7336\nMerzak A, Koocheckpour S, Pilkington GJ (1994) CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res 54:3988–3992\nRadotra B, McCormick D (1997) Glioma invasion in vitro is mediated by CD44-hyaluronan interactions. J Pathol 181:434–438\nGao T, Brognard J, Newton AC (2008) The phosphatase PHLPP controls the cellular levels of protein kinase C. J Biol Chem 283:6300–6311\nKallappagoudar S, Yadav RK, Lowe BR, Partridge JF (2015) Histone H3 mutations--a special role for H3.3 in tumorigenesis? Chromosoma 124:177–189\nMaeda S, Ohka F, Okuno Y, Aoki K, Motomura K, Takeuchi K et al (2020) H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant. Acta Neuropathol Commun 8:8\nAudia JE, Campbell RM (2016) Histone modifications and Cancer. Cold Spring Harb Perspect Biol 8:a019521\nAbdel-Wahab O, Adli M, LaFave LM, Gao J, Hricik T, Shih AH et al (2012) ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 22:180–193\nComet I, Riising EM, Leblanc B, Helin K (2016) Maintaining cell identity: PRC2-mediated regulation of transcription and cancer. Nat Rev Cancer 16:803–810\nJustin N, Zhang Y, Tarricone C, Martin SR, Chen S, Underwood E et al (2016) Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat Commun 7:11316\nBender S, Tang Y, Lindroth AM, Hovestadt V, Jones DT, Kool M et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660–672\nChan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M et al (2013) The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression. Genes Dev 27:985–990\nStafford JM, Lee CH, Voigt P, Descostes N, Saldana-Meyer R, Yu JR et al (2018) Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma. Sci Adv 4:eaau5935\nKornmann M, Hebart H, Danenberg K, Goeb R, Staib L, Kron M et al (2012) Response prediction in metastasised colorectal cancer using intratumoural thymidylate synthase: results of a randomised multicentre trial. Eur J Cancer 48:1443–1451\nRao S, Beckman RA, Riazi S, Yabar CS, Boca SM, Marshall JL et al (2017) Quantification and expert evaluation of evidence for chemopredictive biomarkers to personalize cancer treatment. Oncotarget 8:37923–37934\nShreeram S, Hee WK, Demidov ON, Kek C, Yamaguchi H, Fornace AJ Jr et al (2006) Regulation of ATM\u002Fp53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase. J Exp Med 203:2793–2799\nLi J, Hart RP, Mallimo EM, Swerdel MR, Kusnecov AW, Herrup K (2013) EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia. Nat Neurosci 16:1745–1753\nFuruta T, Takemura H, Liao ZY, Aune GJ, Redon C, Sedelnikova OA et al (2003) Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. J Biol Chem 278:20303–20312\nPark EJ, Chan DW, Park JH, Oettinger MA, Kwon J (2003) DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner. Nucleic Acids Res 31:6819–6827\nDurant ST, Zheng L, Wang Y, Chen K, Zhang L, Zhang T et al (2018) The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models. Sci Adv 4:eaat1719\nRay Chaudhuri A, Nussenzweig A (2017) The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol 18:610–621\nBryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly (ADP-ribose) polymerase. Nature 434:913–917\nLu R, O'Rourke JJ, Sobinoff AP, Allen JAM, Nelson CB, Tomlinson CG et al (2019) The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT). Nat Commun 10:2252\nPan X, Drosopoulos WC, Sethi L, Madireddy A, Schildkraut CL, Zhang D (2017) FANCM, BRCA1, and BLM cooperatively resolve the replication stress at the ALT telomeres. Proc Natl Acad Sci U S A 114:E5940–E59E9\nSilva B, Pentz R, Figueira AM, Arora R, Lee YW, Hodson C et al (2019) FANCM limits ALT activity by restricting telomeric replication stress induced by deregulated BLM and R-loops. Nat Commun 10:2253\nKline CN, Joseph NM, Grenert JP, van Ziffle J, Yeh I, Bastian BC et al (2016) Inactivating MUTYH germline mutations in pediatric patients with high-grade midline gliomas. Neuro-Oncology 18:752–753\nKleczko EK, Heasley LE (2018) Mechanisms of rapid cancer cell reprogramming initiated by targeted receptor tyrosine kinase inhibitors and inherent therapeutic vulnerabilities. Mol Cancer 17:60\nAkhavan D, Pourzia AL, Nourian AA, Williams KJ, Nathanson D, Babic I et al (2013) De-repression of PDGFRbeta transcription promotes acquired resistance to EGFR tyrosine kinase inhibitors in glioblastoma patients. Cancer Discov 3:534–547\nWare KE, Marshall ME, Heasley LR, Marek L, Hinz TK, Hercule P et al (2010) Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression. PLoS One 5:e14117\nKeller S, Schmidt MHH (2017) EGFR and EGFRvIII promote angiogenesis and cell invasion in Glioblastoma: combination therapies for an effective treatment. Int J Mol Sci 18:1295\nMolina JR, Hayashi Y, Stephens C, Georgescu MM (2010) Invasive glioblastoma cells acquire stemness and increased Akt activation. Neoplasia 12:453–463\nPennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM (2003) Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3:347–361\nTakahashi Y, Morales FC, Kreimann EL, Georgescu MM (2006) PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. EMBO J 25:910–920\nKubala MH, DeClerck YA (2019) The plasminogen activator inhibitor-1 paradox in cancer: a mechanistic understanding. Cancer Metastasis Rev 38:483–492\nRhyasen GW, Hattersley MM, Yao Y, Dulak A, Wang W, Petteruti P et al (2016) AZD5153: a novel bivalent BET Bromodomain inhibitor highly active against hematologic malignancies. Mol Cancer Ther 15:2563–2574",{"VOID":479},"10.1186\u002Fs40478-020-00992-9","2024-05-13T05:48:43.149+00:00","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-020-00992-9",[483,498,515,528,543,556,571,586],{"id":484,"sortIndex":19,"researcher":18,"roles":485,"affiliations":486,"properties":495,"displayName":497,"givenName":18,"familyName":18},"dd5b3857-39fd-4f76-9168-b38262d7aaa5",[139],[487],{"id":488,"sortIndex":19,"affiliation":489,"properties":18},"21e88f66-9f0e-4de0-9adb-9e7a76b4cf0e",{"id":488,"createTime":18,"updateTime":18,"relativeEntities":490,"slug":18,"properties":491,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":494,"statistic":18},[],{"title":492},{"VI":493},"NeuroMarkers PLLC, Houston, USA",[],{"title":496},{"VI":497},"M.-M. Georgescu",{"id":499,"sortIndex":94,"researcher":18,"roles":500,"affiliations":501,"properties":510,"displayName":512,"givenName":18,"familyName":18},"cc85f961-5ec2-47c0-8304-1d396d669663",[139],[502],{"id":503,"sortIndex":19,"affiliation":504,"properties":18},"69e13ef3-8f5d-4aab-bf31-9f5aaf2f6d23",{"id":503,"createTime":18,"updateTime":18,"relativeEntities":505,"slug":18,"properties":506,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":509,"statistic":18},[],{"title":507},{"VI":508},"Department of Pathology, Louisiana State University Shreveport, Shreveport, USA",[],{"title":511,"gsAuthor":513},{"VI":512},"M. Z. Islam",{"VOID":514},"[\"tEHswKsAAAAJ\"]",{"id":516,"sortIndex":96,"researcher":18,"roles":517,"affiliations":518,"properties":525,"displayName":527,"givenName":18,"familyName":18},"42b673fa-7d7c-485d-81c1-3820b2433f73",[139],[519],{"id":503,"sortIndex":19,"affiliation":520,"properties":18},{"id":503,"createTime":18,"updateTime":18,"relativeEntities":521,"slug":18,"properties":522,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":524,"statistic":18},[],{"title":523},{"VI":508},[],{"title":526},{"VI":527},"Y. Li",{"id":529,"sortIndex":101,"researcher":18,"roles":530,"affiliations":531,"properties":540,"displayName":542,"givenName":18,"familyName":18},"768f62fe-4914-4239-a2dd-766f3a8a2a8e",[139],[532],{"id":533,"sortIndex":19,"affiliation":534,"properties":18},"de474fce-838f-4740-9951-d8f042e76e08",{"id":533,"createTime":18,"updateTime":18,"relativeEntities":535,"slug":18,"properties":536,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":539,"statistic":18},[],{"title":537},{"VI":538},"Department of Microbiology and Immunology, Louisiana State University Shreveport, Shreveport, USA",[],{"title":541},{"VI":542},"M. L. Circu",{"id":544,"sortIndex":100,"researcher":18,"roles":545,"affiliations":546,"properties":553,"displayName":555,"givenName":18,"familyName":18},"57cb8965-9ec9-4022-a6f7-52e0aab3c220",[139],[547],{"id":503,"sortIndex":19,"affiliation":548,"properties":18},{"id":503,"createTime":18,"updateTime":18,"relativeEntities":549,"slug":18,"properties":550,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":552,"statistic":18},[],{"title":551},{"VI":508},[],{"title":554},{"VI":555},"J. Traylor",{"id":557,"sortIndex":99,"researcher":18,"roles":558,"affiliations":559,"properties":568,"displayName":570,"givenName":18,"familyName":18},"7105be6c-469d-4c86-bd18-c38dea3c67ae",[139],[560],{"id":561,"sortIndex":19,"affiliation":562,"properties":18},"84ded26e-cb8b-44f9-89fd-cdd86805e29d",{"id":561,"createTime":18,"updateTime":18,"relativeEntities":563,"slug":18,"properties":564,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":567,"statistic":18},[],{"title":565},{"VI":566},"Department of Neurosurgery, Louisiana State University Shreveport, Shreveport, USA",[],{"title":569},{"VI":570},"C. M. Notarianni",{"id":572,"sortIndex":285,"researcher":18,"roles":573,"affiliations":574,"properties":583,"displayName":585,"givenName":18,"familyName":18},"b258f289-3cf3-4939-bfea-46b7ac436c9c",[139],[575],{"id":576,"sortIndex":19,"affiliation":577,"properties":18},"c995ef47-19cb-4de9-bd14-111b36d70b52",{"id":576,"createTime":18,"updateTime":18,"relativeEntities":578,"slug":18,"properties":579,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":582,"statistic":18},[],{"title":580},{"VI":581},"Department of Pediatrics, University of California, San Francisco, San Francisco USA",[],{"title":584},{"VI":585},"C. N. Kline",{"id":587,"sortIndex":308,"researcher":18,"roles":588,"affiliations":589,"properties":598,"displayName":600,"givenName":18,"familyName":18},"edb02b92-903d-40ce-9e3c-ad6f1035011a",[139],[590],{"id":591,"sortIndex":19,"affiliation":592,"properties":18},"5677e6e2-ff07-4c9b-b5b2-37374fae9e3f",{"id":591,"createTime":18,"updateTime":18,"relativeEntities":593,"slug":18,"properties":594,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":597,"statistic":18},[],{"title":595},{"VI":596},"Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, USA",[],{"title":599},{"VI":600},"D. K. Burns",{"url":481,"publisher":602,"properties":651},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":603,"slug":10,"properties":604,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":607,"manageAffiliations":620,"indexDatabases":631,"url":91,"thumbnailPath":18,"statistic":646,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":605,"title":606},{"VOID":13},{"EN":15},[608,612,616],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":609,"label":610,"description":611,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":613,"label":614,"description":615,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":617,"label":618,"description":619,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[621,626],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":622,"slug":18,"properties":623,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":625,"statistic":18},[],{"title":624},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":627,"slug":18,"properties":628,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":630,"statistic":18},[],{"title":629},{"EN":52},[],[632,639],{"id":56,"indexDatabase":633,"url":69,"indexYears":18,"academicFieldIds":638,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":634,"label":635,"description":636,"key":65,"publicationTags":637,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":640,"url":84,"indexYears":85,"academicFieldIds":645,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":641,"label":642,"description":643,"key":81,"publicationTags":644,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":647,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":648,"totalCitation":102,"totalCitationByYear":649,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":650,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":652,"volume":654},{"VOID":653},"1-17",{"VOID":655},"8",38,{"total":656,"publishYear":658,"statisticByYear":659},2020,{"2021":100,"2022":354,"2023":333,"2024":285,"2025":99,"2026":285},"2020-07-17","DONE_ANALYZE_CITATION","2026-07-27T03:29:17.180+00:00",[67,90],{"id":665,"createTime":666,"updateTime":667,"relativeEntities":668,"slug":669,"properties":670,"entityType":128,"verifyStatus":129,"verifyTime":681,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":682,"fullTextUrl":683,"authors":684,"publicationType":403,"publisherRelationship":715,"citationCount":18,"citationInfo":18,"publishDate":771,"publishYear":658,"citationAnalyzeStatus":17,"lastCitationAnalyze":772,"indexDatabases":773,"openAccess":18,"references":18,"isForceReanalyzing":462},"37524150-59ff-450b-8163-1cff7801226d","2024-01-30T17:04:51.307+00:00","2026-07-21T11:08:16.812+00:00",[],"Meta-analysis-of-human-prefrontal-cortex-reveals-activation-of-GFAP-and-decline-of-synaptic-transmission-in-the-aging-brain",{"abstract":671,"title":673,"gsPaper":675,"references":677,"doi":679},{"EN":672},"Despite ongoing research efforts, mechanisms of brain aging are still enigmatic and need to be elucidated for a better understanding of age-associated cognitive decline. The aim of this study is to investigate aging in the prefrontal cortex region of human brain in a meta-analysis of transcriptome datasets. We analyzed 591 gene expression datasets pertaining to female and male human prefrontal cortex biopsies of distinct ages. We used hierarchical clustering and principal component analysis (PCA) to determine the influence of sex and age on global transcriptome levels. In sex-specific analysis we identified genes correlating with age and differentially expressed between groups of young, middle-aged and aged. Pathways and gene ontologies (GOs) over-represented in the resulting gene sets were calculated. Potential causal relationships between genes and between GOs were explored employing the Granger test of gene expression time series over the range of ages. The most outstanding results were the age-related decline of synaptic transmission and activated expression of glial fibrillary acidic protein (GFAP) in both sexes. We found an antagonistic relationship between calcium\u002Fcalmodulin dependent protein kinase IV (CAMK4) and GFAP which may include regulatory mechanisms involving cAMP responsive element binding protein (CREB) and mitogen-activated protein kinase (MAPK, alias ERK). Common to both sexes was a decline in synaptic transmission, neurogenesis and an increased base-level of inflammatory and immune-related processes. Furthermore, we detected differences in dendritic spine morphogenesis, catecholamine signaling and cellular responses to external stimuli, particularly to metal (Zinc and cadmium) ions which were higher in female brains.",{"EN":674},"Meta-analysis of human prefrontal cortex reveals activation of GFAP and decline of synaptic transmission in the aging brain",{"VOID":676},"[\"4915278625655414182\"]",{"VOID":678},"citation_journal_title=Front Endocrinol; citation_title=Insulin, aging, and the brain: mechanisms and implications; citation_author=AA Akintola, D Heemst; citation_volume=6; citation_publication_date=2015; citation_pages=13; citation_doi=10.3389\u002Ffendo.2015.00013; citation_id=CR1\ncitation_journal_title=J Comp Neurol; citation_title=Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats; citation_author=J Altman, GD Das; citation_volume=124; citation_publication_date=1965; citation_pages=319-335; citation_doi=10.1002\u002Fcne.901240303; citation_id=CR2\ncitation_journal_title=Nat Rev Neurol; citation_title=Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums; citation_author=SE Arnold, Z Arvanitakis, SL Macauley-Rambach, AM Koenig, H-Y Wang, RS Ahima, S Craft, S Gandy, C Buettner, LE Stoeckel, DM Holtzman, DM Nathan; citation_volume=14; citation_publication_date=2018; citation_pages=168-181; citation_doi=10.1038\u002Fnrneurol.2017.185; citation_id=CR3\ncitation_journal_title=J Neurosci Res; citation_title=Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia; citation_author=MR Barnes, J Huxley-Jones, PR Maycox, M Lennon, A Thornber, F Kelly, S Bates, A Taylor, J Reid, N Jones, J Schroeder, CA Scorer, C Davies, JJ Hagan, JNC Kew, C Angelinetta, T Akbar, S Hirsch, AM Mortimer, TRE Barnes, J Belleroche; citation_volume=89; citation_publication_date=2011; citation_pages=1218-1227; citation_doi=10.1002\u002Fjnr.22647; citation_id=CR4\ncitation_journal_title=Cell; citation_title=CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression; citation_author=H Bito, K Deisseroth, RW Tsien; citation_volume=87; citation_publication_date=1996; citation_pages=1203-1214; citation_doi=10.1016\u002Fs0092-8674(00)81816-4; citation_id=CR5\ncitation_journal_title=Curr Opin Neurobiol; citation_title=Do thin spines learn to be mushroom spines that remember?; citation_author=J Bourne, KM Harris; citation_volume=17; citation_publication_date=2007; citation_pages=381-386; citation_doi=10.1016\u002Fj.conb.2007.04.009; citation_id=CR6\ncitation_journal_title=Biogerontology; citation_title=Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging; citation_author=TC Brink, L Demetrius, H Lehrach, J Adjaye; citation_volume=10; citation_publication_date=2009; citation_pages=549-564; citation_doi=10.1007\u002Fs10522-008-9197-8; citation_id=CR7\ncitation_journal_title=Biogerontology; citation_title=Activation of the immune response is a key feature of aging in mice; citation_author=TC Brink, C Regenbrecht, L Demetrius, H Lehrach, J Adjaye; citation_volume=10; citation_publication_date=2009; citation_pages=721-734; citation_doi=10.1007\u002Fs10522-009-9219-1; citation_id=CR8\ncitation_journal_title=Nucleic Acids Res; citation_title=The BioGRID interaction database: 2017 update; citation_author=A Chatr-Aryamontri, R Oughtred, L Boucher, J Rust, C Chang, NK Kolas, L O’Donnell, S Oster, C Theesfeld, A Sellam, C Stark, B-J Breitkreutz, K Dolinski, M Tyers; citation_volume=45; citation_publication_date=2017; citation_pages=D369-D379; citation_doi=10.1093\u002Fnar\u002Fgkw1102; citation_id=CR9\ncitation_journal_title=Proc Natl Acad Sci U S A; citation_title=Effects of aging on circadian patterns of gene expression in the human prefrontal cortex; citation_author=C-Y Chen, RW Logan, T Ma, DA Lewis, GC Tseng, E Sibille, CA McClung; citation_volume=113; citation_publication_date=2016; citation_pages=206-211; citation_doi=10.1073\u002Fpnas.1508249112; citation_id=CR10\ncitation_journal_title=Proc Natl Acad Sci U S A; citation_title=Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation; citation_author=H Cheng, H Xuan, CD Green, Y Han, N Sun, H Shen, J McDermott, DA Bennett, F Lan, J-DJ Han; citation_volume=115; citation_publication_date=2018; citation_pages=7611-7616; citation_doi=10.1073\u002Fpnas.1800656115; citation_id=CR11\ncitation_journal_title=InterJ Complex Syst; citation_title=The igraph software package for complex network research; citation_author=G Csardi, T Nepusz; citation_volume=1695; citation_publication_date=2006; citation_pages=1-9; citation_id=CR12\ncitation_journal_title=J Diabetes Sci Technol; citation_title=Alzheimer’s disease is type 3 diabetes--evidence reviewed; citation_author=SM Monte, JR Wands; citation_volume=2; citation_publication_date=2008; citation_pages=1101-1113; citation_doi=10.1177\u002F193229680800200619; citation_id=CR13\ncitation_journal_title=Nat Med; citation_title=Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease; citation_author=J Khoury, M Toft, SE Hickman, TK Means, K Terada, C Geula, AD Luster; citation_volume=13; citation_publication_date=2007; citation_pages=432-438; citation_doi=10.1038\u002Fnm1555; citation_id=CR14\ncitation_journal_title=J Neurochem; citation_title=MCP-1 (CCL2) protects human neurons and astrocytes from NMDA or HIV-tat-induced apoptosis; citation_author=EA Eugenin, TG D’Aversa, L Lopez, TM Calderon, JW Berman; citation_volume=85; citation_publication_date=2003; citation_pages=1299-1311; citation_doi=10.1046\u002Fj.1471-4159.2003.01775.x; citation_id=CR15\ncitation_journal_title=Bioinformatics; citation_title=Using GOstats to test gene lists for GO term association; citation_author=S Falcon, R Gentleman; citation_volume=23; citation_publication_date=2007; citation_pages=257-258; citation_doi=10.1093\u002Fbioinformatics\u002Fbtl567; citation_id=CR16\ncitation_journal_title=J Neural Transm (Vienna); citation_title=Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease; citation_author=L Frölich, D Blum-Degen, HG Bernstein, S Engelsberger, J Humrich, S Laufer, D Muschner, A Thalheimer, A Türk, S Hoyer, R Zöchling, KW Boissl, K Jellinger, P Riederer; citation_volume=105; citation_publication_date=1998; citation_pages=423-438; citation_doi=10.1007\u002Fs007020050068; citation_id=CR17\ncitation_journal_title=Adv Exp Med Biol; citation_title=Cyclic AMP signaling in pancreatic islets; citation_author=B Furman, WK Ong, NJ Pyne; citation_volume=654; citation_publication_date=2010; citation_pages=281-304; citation_doi=10.1007\u002F978-90-481-3271-3_13; citation_id=CR18\ncitation_journal_title=Bioinformatics; citation_title=Dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering; citation_author=T Galili; citation_volume=31; citation_publication_date=2015; citation_pages=3718-3720; citation_doi=10.1093\u002Fbioinformatics\u002Fbtv428; citation_id=CR19\ncitation_journal_title=Horm Behav; citation_title=Testosterone regulates the density of dendritic spines in the male preoptic area; citation_author=T Garelick, J Swann; citation_volume=65; citation_publication_date=2014; citation_pages=249-253; citation_doi=10.1016\u002Fj.yhbeh.2014.01.008; citation_id=CR20\ncitation_journal_title=Genome Biol; citation_title=Bioconductor: open software development for computational biology and bioinformatics; citation_author=RC Gentleman, VJ Carey, DM Bates, B Bolstad, M Dettling, S Dudoit, B Ellis, L Gautier, Y Ge, J Gentry, K Hornik, T Hothorn, W Huber, S Iacus, R Irizarry, F Leisch, C Li, M Maechler, AJ Rossini, G Sawitzki, C Smith, G Smyth, L Tierney, JYH Yang, J Zhang; citation_volume=5; citation_publication_date=2004; citation_pages=R80; citation_doi=10.1186\u002Fgb-2004-5-10-r80; citation_id=CR21\ncitation_journal_title=Econometrica; citation_title=Investigating causal relations by econometric models and cross-spectral methods; citation_author=CWJ Granger; citation_volume=37; citation_publication_date=1969; citation_pages=424-438; citation_doi=10.2307\u002F1912791; citation_id=CR22\ncitation_journal_title=Diabetes; citation_title=Insulin regulates brain function, but how does it get there?; citation_author=SM Gray, RI Meijer, EJ Barrett; citation_volume=63; citation_publication_date=2014; citation_pages=3992-3997; citation_doi=10.2337\u002Fdb14-0340; citation_id=CR23\ncitation_journal_title=PLoS One; citation_title=Inference of cell type content from human brain transcriptomic datasets illuminates the effects of age, manner of death, dissection, and psychiatric diagnosis; citation_author=MH Hagenauer, A Schulmann, JZ Li, MP Vawter, DM Walsh, RC Thompson, CA Turner, WE Bunney, RM Myers, JD Barchas, AF Schatzberg, SJ Watson, H Akil; citation_volume=13; citation_publication_date=2018; citation_pages=e0200003; citation_doi=10.1371\u002Fjournal.pone.0200003; citation_id=CR24\ncitation_journal_title=Annu Rev Neurosci; citation_title=Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function; citation_author=KM Harris, SB Kater; citation_volume=17; citation_publication_date=1994; citation_pages=341-371; citation_doi=10.1146\u002Fannurev.ne.17.030194.002013; citation_id=CR25\ncitation_journal_title=Trends Cell Biol; citation_title=Taking a “good” look at free radicals in the aging process; citation_author=S Hekimi, J Lapointe, Y Wen; citation_volume=21; citation_publication_date=2011; citation_pages=569-576; citation_doi=10.1016\u002Fj.tcb.2011.06.008; citation_id=CR26\ncitation_journal_title=Nat Rev Neurosci; citation_title=Immune attack: the role of inflammation in Alzheimer disease; citation_author=FL Heppner, RM Ransohoff, B Becher; citation_volume=16; citation_publication_date=2015; citation_pages=358-372; citation_doi=10.1038\u002Fnrn3880; citation_id=CR27\ncitation_journal_title=J Stat Softw; citation_title=Automatic time series forecasting: the forecast package for R; citation_author=RJ Hyndman, Y Khandakar; citation_volume=26; citation_publication_date=2008; citation_pages=1-22; citation_id=CR28\ncitation_journal_title=Nucleic Acids Res; citation_title=KEGG: new perspectives on genomes, pathways, diseases and drugs; citation_author=M Kanehisa, M Furumichi, M Tanabe, Y Sato, K Morishima; citation_volume=45; citation_publication_date=2017; citation_pages=D353-D361; citation_doi=10.1093\u002Fnar\u002Fgkw1092; citation_id=CR29\ncitation_title=Practical guide to cluster analysis in R: unsupervised machine learning, edition 1; citation_publication_date=2017; citation_id=CR30; citation_author=A Kassambara; citation_publisher=STHDA\ncitation_journal_title=Diabetes Obes Metab; citation_title=Impact of nitric oxide on metabolism in health and age-related disease; citation_author=AB Knott, E Bossy-Wetzel; citation_volume=12; citation_issue=Suppl 2; citation_publication_date=2010; citation_pages=126-133; citation_doi=10.1111\u002Fj.1463-1326.2010.01267.x; citation_id=CR31\ncitation_journal_title=Brain Behav Immun; citation_title=Neurogenesis, inflammation and behavior; citation_author=RA Kohman, JS Rhodes; citation_volume=27; citation_publication_date=2013; citation_pages=22-32; citation_doi=10.1016\u002Fj.bbi.2012.09.003; citation_id=CR32\ncitation_journal_title=Front Aging Neurosci; citation_title=Susceptibility to calcium dysregulation during brain aging; citation_author=A Kumar, K Bodhinathan, TC Foster; citation_volume=1; citation_publication_date=2009; citation_pages=2; citation_doi=10.3389\u002Fneuro.24.002.2009; citation_id=CR33\ncitation_journal_title=PLoS One; citation_title=STEP levels are unchanged in pre-frontal cortex and associative striatum in post-mortem human brain samples from subjects with schizophrenia, bipolar disorder and major depressive disorder; citation_author=TA Lanz, JJ Joshi, V Reinhart, K Johnson, LE Grantham, D Volfson; citation_volume=10; citation_publication_date=2015; citation_pages=e0121744; citation_doi=10.1371\u002Fjournal.pone.0121744; citation_id=CR34\ncitation_journal_title=Cell; citation_title=The hallmarks of aging; citation_author=C López-Otín, MA Blasco, L Partridge, M Serrano, G Kroemer; citation_volume=153; citation_publication_date=2013; citation_pages=1194-1217; citation_doi=10.1016\u002Fj.cell.2013.05.039; citation_id=CR35\ncitation_journal_title=Nature; citation_title=REST and stress resistance in ageing and Alzheimer’s disease; citation_author=T Lu, L Aron, J Zullo, Y Pan, H Kim, Y Chen, T-H Yang, H-M Kim, D Drake, XS Liu, DA Bennett, MP Colaiácovo, BA Yankner; citation_volume=507; citation_publication_date=2014; citation_pages=448-454; citation_doi=10.1038\u002Fnature13163; citation_id=CR36\ncitation_journal_title=Science; citation_title=Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain; citation_author=LN Manganas, X Zhang, Y Li, RD Hazel, SD Smith, ME Wagshul, F Henn, H Benveniste, PM Djuric, G Enikolopov, M Maletic-Savatic; citation_volume=318; citation_publication_date=2007; citation_pages=980-985; citation_doi=10.1126\u002Fscience.1147851; citation_id=CR37\ncitation_journal_title=Prog Neurobiol; citation_title=GFAP in health and disease; citation_author=J Middeldorp, EM Hol; citation_volume=93; citation_publication_date=2011; citation_pages=421-443; citation_doi=10.1016\u002Fj.pneurobio.2011.01.005; citation_id=CR38\ncitation_journal_title=Nat Rev Neurosci; citation_title=The ageing cortical synapse: hallmarks and implications for cognitive decline; citation_author=JH Morrison, MG Baxter; citation_volume=13; citation_publication_date=2012; citation_pages=240-250; citation_doi=10.1038\u002Fnrn3200; citation_id=CR39\ncitation_journal_title=J Neurosci; citation_title=Altered synaptic dynamics during normal brain aging; citation_author=R Mostany, JE Anstey, KL Crump, B Maco, G Knott, C Portera-Cailliau; citation_volume=33; citation_publication_date=2013; citation_pages=4094-4104; citation_doi=10.1523\u002FJNEUROSCI.4825-12.2013; citation_id=CR40\ncitation_journal_title=Brain Res; citation_title=Molecular profiles of schizophrenia in the CNS at different stages of illness; citation_author=S Narayan, B Tang, SR Head, TJ Gilmartin, JG Sutcliffe, B Dean, EA Thomas; citation_volume=1239; citation_publication_date=2008; citation_pages=235-248; citation_doi=10.1016\u002Fj.brainres.2008.08.023; citation_id=CR41\ncitation_journal_title=Cell; citation_title=Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases; citation_author=S-J Park, F Ahmad, A Philp, K Baar, T Williams, H Luo, H Ke, H Rehmann, R Taussig, AL Brown, MK Kim, MA Beaven, AB Burgin, V Manganiello, JH Chung; citation_volume=148; citation_publication_date=2012; citation_pages=421-433; citation_doi=10.1016\u002Fj.cell.2012.01.017; citation_id=CR42\ncitation_journal_title=Mol Neurodegener; citation_title=Downregulation of CREB expression in Alzheimer’s brain and in Aβ-treated rat hippocampal neurons; citation_author=S Pugazhenthi, M Wang, S Pham, C-I Sze, CB Eckman; citation_volume=6; citation_publication_date=2011; citation_pages=60; citation_doi=10.1186\u002F1750-1326-6-60; citation_id=CR43\ncitation_journal_title=Nature; citation_title=Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid; citation_author=A Schmidt, M Wolde, C Thiele, W Fest, H Kratzin, AV Podtelejnikov, W Witke, WB Huttner, HD Söling; citation_volume=401; citation_publication_date=1999; citation_pages=133-141; citation_doi=10.1038\u002F43613; citation_id=CR44\ncitation_journal_title=Psychoneuroendocrinology; citation_title=Estradiol and the relationship between dendritic spines, NR2B containing NMDA receptors, and the magnitude of long-term potentiation at hippocampal CA3-CA1 synapses; citation_author=CC Smith, LC Vedder, LL McMahon; citation_volume=34; citation_issue=Suppl 1; citation_publication_date=2009; citation_pages=S130-S142; citation_doi=10.1016\u002Fj.psyneuen.2009.06.003; citation_id=CR45\ncitation_journal_title=Acta Neuropathol; citation_title=Astrocytes: biology and pathology; citation_author=MV Sofroniew, HV Vinters; citation_volume=119; citation_publication_date=2010; citation_pages=7-35; citation_doi=10.1007\u002Fs00401-009-0619-8; citation_id=CR46\ncitation_journal_title=Neuroscience; citation_title=IL-1β induces GFAP expression in vitro and in vivo and protects neurons from traumatic injury-associated apoptosis in rat brain striatum via NFκB\u002FCa2+-calmodulin\u002FERK mitogen-activated protein kinase signaling pathway; citation_author=C Sticozzi, G Belmonte, A Meini, P Carbotti, G Grasso, M Palmi; citation_volume=252; citation_publication_date=2013; citation_pages=367-383; citation_doi=10.1016\u002Fj.neuroscience.2013.07.061; citation_id=CR47\ncitation_journal_title=BMC Bioinformatics; citation_title=Unlocking the potential of publicly available microarray data using inSilicoDb and inSilicoMerging R\u002Fbioconductor packages; citation_author=J Taminau, S Meganck, C Lazar, D Steenhoff, A Coletta, C Molter, R Duque, V Schaetzen, DY Weiss Solís, H Bersini, A Nowé; citation_volume=13; citation_publication_date=2012; citation_pages=335; citation_doi=10.1186\u002F1471-2105-13-335; citation_id=CR48\ncitation_journal_title=Sci Rep; citation_title=Cyclic AMP mimics the anti-ageing effects of calorie restriction by up-regulating Sirtuin; citation_author=Z Wang, L Zhang, Y Liang, C Zhang, Z Xu, L Zhang, R Fuji, W Mu, L Li, J Jiang, Y Ju, Z Wang; citation_volume=5; citation_publication_date=2015; citation_pages=1-10; citation_doi=10.1038\u002Fsrep12012; citation_id=CR49\ncitation_title=R package “corrplot”: visualization of a correlation matrix; citation_publication_date=2017; citation_id=CR50; citation_author=T Wei; citation_author=V Simko\ncitation_title=Ggplot2: elegant graphics for data analysis; citation_publication_date=2009; citation_id=CR51; citation_author=H Wickham; citation_publisher=Springer\ncitation_journal_title=J Neurosci; citation_title=Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism; citation_author=CS Woolley, BS McEwen; citation_volume=14; citation_publication_date=1994; citation_pages=7680-7687; citation_doi=10.1523\u002FJNEUROSCI.14-12-07680.1994; citation_id=CR52\ncitation_journal_title=J Alzheimers Dis; citation_title=Meta-analysis of transcriptome data related to hippocampus biopsies and iPSC-derived neuronal cells from alzheimer’s disease patients reveals an association with FOXA1 and FOXA2 gene regulatory networks; citation_author=W Wruck, F Schröter, J Adjaye; citation_volume=50; citation_publication_date=2016; citation_pages=1065-1082; citation_doi=10.3233\u002FJAD-150733; citation_id=CR53\ncitation_journal_title=Proc Natl Acad Sci U S A; citation_title=Activity-dependent CREB phosphorylation: convergence of a fast, sensitive calmodulin kinase pathway and a slow, less sensitive mitogen-activated protein kinase pathway; citation_author=GY Wu, K Deisseroth, RW Tsien; citation_volume=98; citation_publication_date=2001; citation_pages=2808-2813; citation_doi=10.1073\u002Fpnas.051634198; citation_id=CR54\ncitation_journal_title=Acta Neuropathol Commun; citation_title=Transcriptomopathies of pre- and post-symptomatic frontotemporal dementia-like mice with TDP-43 depletion in forebrain neurons; citation_author=L-S Wu, W-C Cheng, C-Y Chen, M-C Wu, Y-C Wang, Y-H Tseng, T-J Chuang, C-KJ Shen; citation_volume=7; citation_publication_date=2019; citation_pages=50; citation_doi=10.1186\u002Fs40478-019-0674-x; citation_id=CR55\ncitation_journal_title=R News; citation_title=Diagnostic checking in regression relationships; citation_author=A Zeileis, T Hothorn; citation_volume=2; citation_publication_date=2002; citation_pages=7-10; citation_id=CR56",{"VOID":680},"10.1186\u002Fs40478-020-00907-8","2024-06-26T19:59:50.745+00:00","https:\u002F\u002Flink.springer.com\u002Farticle\u002F10.1186\u002Fs40478-020-00907-8","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Fcounter\u002Fpdf\u002F10.1186\u002Fs40478-020-00907-8",[685,702],{"id":686,"sortIndex":19,"researcher":18,"roles":687,"affiliations":688,"properties":697,"displayName":699,"givenName":18,"familyName":18},"8c8ed706-a8c7-4874-9e95-fdfdb86697f1",[139],[689],{"id":690,"sortIndex":19,"affiliation":691,"properties":18},"49fb0295-38c8-44f8-91d2-81a46a95c64a",{"id":690,"createTime":18,"updateTime":18,"relativeEntities":692,"slug":18,"properties":693,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":696,"statistic":18},[],{"title":694},{"EN":695},"Institute for Stem Cell Research and Regenerative Medicine, Medical faculty, Heinrich-Heine University, Düsseldorf, Germany",[],{"title":698,"gsAuthor":700},{"VI":699},"Wruck, Wasco",{"VOID":701},"[\"VjH8r9oAAAAJ\"]",{"id":703,"sortIndex":94,"researcher":18,"roles":704,"affiliations":705,"properties":712,"displayName":714,"givenName":18,"familyName":18},"643c7ab0-945c-479f-927b-acf2ebfb4eaa",[139],[706],{"id":690,"sortIndex":19,"affiliation":707,"properties":18},{"id":690,"createTime":18,"updateTime":18,"relativeEntities":708,"slug":18,"properties":709,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":711,"statistic":18},[],{"title":710},{"EN":695},[],{"title":713},{"VI":714},"Adjaye, James",{"url":682,"publisher":716,"properties":765},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":717,"slug":10,"properties":718,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":721,"manageAffiliations":734,"indexDatabases":745,"url":91,"thumbnailPath":18,"statistic":760,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":719,"title":720},{"VOID":13},{"EN":15},[722,726,730],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":723,"label":724,"description":725,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":727,"label":728,"description":729,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":731,"label":732,"description":733,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[735,740],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":736,"slug":18,"properties":737,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":739,"statistic":18},[],{"title":738},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":741,"slug":18,"properties":742,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":744,"statistic":18},[],{"title":743},{"EN":52},[],[746,753],{"id":56,"indexDatabase":747,"url":69,"indexYears":18,"academicFieldIds":752,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":748,"label":749,"description":750,"key":65,"publicationTags":751,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":754,"url":84,"indexYears":85,"academicFieldIds":759,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":755,"label":756,"description":757,"key":81,"publicationTags":758,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":761,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":762,"totalCitation":102,"totalCitationByYear":763,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":764,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"issue":766,"pages":768,"volume":770},{"VOID":767},"1",{"VOID":769},"1-18",{"VOID":655},"2020-12-01","2026-07-21T11:08:16.811+00:00",[67,90],{"id":775,"createTime":776,"updateTime":777,"relativeEntities":778,"slug":779,"properties":780,"entityType":128,"verifyStatus":129,"verifyTime":789,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":790,"fullTextUrl":18,"authors":791,"publicationType":403,"publisherRelationship":952,"citationCount":18,"citationInfo":18,"publishDate":1006,"publishYear":460,"citationAnalyzeStatus":1007,"lastCitationAnalyze":1008,"indexDatabases":1009,"openAccess":18,"references":18,"isForceReanalyzing":462},"1f99bf18-1ed5-4f02-8160-8f8b784a02dc","2023-12-07T20:52:26.043+00:00","2026-07-20T02:00:09.289+00:00",[],"Correction-to-Higher-angiotensin-converting-enzyme-2-ACE2-levels-in-the-brain-of-individuals-with-Alzheimer-s-disease",{"title":781,"gsPaper":783,"references":785,"doi":787},{"EN":782},"Correction to: Higher angiotensin‑converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease",{"VOID":784},"[]",{"VOID":786},"Reveret L, Leclerc M, Emond V et al (2023) Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s Disease. acta Neuropathol Commun 11:159. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs40478-023-01647-1",{"VOID":788},"10.1186\u002Fs40478-023-01678-8","2024-06-26T09:05:06.797+00:00","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-023-01678-8",[792,816,836,849,862,875,895,910,932],{"id":793,"sortIndex":19,"researcher":18,"roles":794,"affiliations":795,"properties":813,"displayName":815,"givenName":18,"familyName":18},"fa5e1b34-a6e8-4659-b83f-0ccea8727660",[139],[796,804],{"id":797,"sortIndex":19,"affiliation":798,"properties":18},"0dcedc4d-d119-44ad-875c-98be5f26a46f",{"id":797,"createTime":18,"updateTime":18,"relativeEntities":799,"slug":18,"properties":800,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":803,"statistic":18},[],{"title":801},{"VI":802},"Faculty of Pharmacy, Laval University, Quebec, Canada",[],{"id":805,"sortIndex":94,"affiliation":806,"properties":812},"a5540a8f-83b7-47c6-8033-e357c4accba0",{"id":805,"createTime":18,"updateTime":18,"relativeEntities":807,"slug":18,"properties":808,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":811,"statistic":18},[],{"title":809},{"VI":810},"CHU de Quebec Research Center, Quebec, Canada",[],{},{"title":814},{"VI":815},"Louise Reveret",{"id":817,"sortIndex":94,"researcher":18,"roles":818,"affiliations":819,"properties":833,"displayName":835,"givenName":18,"familyName":18},"6d8d8d6e-5e24-4c1c-8229-bca35858997d",[139],[820,826],{"id":797,"sortIndex":19,"affiliation":821,"properties":18},{"id":797,"createTime":18,"updateTime":18,"relativeEntities":822,"slug":18,"properties":823,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":825,"statistic":18},[],{"title":824},{"VI":802},[],{"id":805,"sortIndex":94,"affiliation":827,"properties":832},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":828,"slug":18,"properties":829,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":831,"statistic":18},[],{"title":830},{"VI":810},[],{},{"title":834},{"VI":835},"Manon Leclerc",{"id":837,"sortIndex":96,"researcher":18,"roles":838,"affiliations":839,"properties":846,"displayName":848,"givenName":18,"familyName":18},"562ca70f-eb85-4da1-b58e-95d11803fe68",[139],[840],{"id":805,"sortIndex":19,"affiliation":841,"properties":18},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":842,"slug":18,"properties":843,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":845,"statistic":18},[],{"title":844},{"VI":810},[],{"title":847},{"VI":848},"Vincent Emond",{"id":850,"sortIndex":101,"researcher":18,"roles":851,"affiliations":852,"properties":859,"displayName":861,"givenName":18,"familyName":18},"26826ccd-ba3d-4a8a-9f1b-1ac88a190f6f",[139],[853],{"id":805,"sortIndex":19,"affiliation":854,"properties":18},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":855,"slug":18,"properties":856,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":858,"statistic":18},[],{"title":857},{"VI":810},[],{"title":860},{"VI":861},"Cyntia Tremblay",{"id":863,"sortIndex":100,"researcher":18,"roles":864,"affiliations":865,"properties":872,"displayName":874,"givenName":18,"familyName":18},"58a7e11b-2bf6-46a9-92d2-ee9f818b5a2d",[139],[866],{"id":805,"sortIndex":19,"affiliation":867,"properties":18},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":868,"slug":18,"properties":869,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":871,"statistic":18},[],{"title":870},{"VI":810},[],{"title":873},{"VI":874},"Andréanne Loiselle",{"id":876,"sortIndex":99,"researcher":18,"roles":877,"affiliations":878,"properties":892,"displayName":894,"givenName":18,"familyName":18},"5387be3b-0420-4147-9c62-920521a05321",[139],[879,885],{"id":797,"sortIndex":19,"affiliation":880,"properties":18},{"id":797,"createTime":18,"updateTime":18,"relativeEntities":881,"slug":18,"properties":882,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":884,"statistic":18},[],{"title":883},{"VI":802},[],{"id":805,"sortIndex":94,"affiliation":886,"properties":891},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":887,"slug":18,"properties":888,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":890,"statistic":18},[],{"title":889},{"VI":810},[],{},{"title":893},{"VI":894},"Philippe Bourassa",{"id":896,"sortIndex":285,"researcher":18,"roles":897,"affiliations":898,"properties":907,"displayName":909,"givenName":18,"familyName":18},"48529317-c6a7-4b89-b576-386e8b5a7bbf",[139],[899],{"id":900,"sortIndex":19,"affiliation":901,"properties":18},"72931f8f-b3ab-4b69-80dd-319271ee8ccc",{"id":900,"createTime":18,"updateTime":18,"relativeEntities":902,"slug":18,"properties":903,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":906,"statistic":18},[],{"title":904},{"VI":905},"Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, USA",[],{"title":908},{"VI":909},"David A. Bennett",{"id":911,"sortIndex":308,"researcher":18,"roles":912,"affiliations":913,"properties":929,"displayName":931,"givenName":18,"familyName":18},"30cadec6-2b4c-4227-90ce-17403851a98b",[139],[914,920],{"id":805,"sortIndex":19,"affiliation":915,"properties":18},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":916,"slug":18,"properties":917,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":919,"statistic":18},[],{"title":918},{"VI":810},[],{"id":921,"sortIndex":94,"affiliation":922,"properties":928},"1ea63861-dbfe-4d1a-bdb8-c9f5303073da",{"id":921,"createTime":18,"updateTime":18,"relativeEntities":923,"slug":18,"properties":924,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":927,"statistic":18},[],{"title":925},{"EN":926},"Faculty of Medicine, Laval University, Quebec, Canada",[],{},{"title":930},{"VI":931},"Sébastien S. Hébert",{"id":933,"sortIndex":333,"researcher":18,"roles":934,"affiliations":935,"properties":949,"displayName":951,"givenName":18,"familyName":18},"c2a1d98d-5209-4209-afa2-48c4d06984dd",[139],[936,942],{"id":797,"sortIndex":19,"affiliation":937,"properties":18},{"id":797,"createTime":18,"updateTime":18,"relativeEntities":938,"slug":18,"properties":939,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":941,"statistic":18},[],{"title":940},{"VI":802},[],{"id":805,"sortIndex":94,"affiliation":943,"properties":948},{"id":805,"createTime":18,"updateTime":18,"relativeEntities":944,"slug":18,"properties":945,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":947,"statistic":18},[],{"title":946},{"VI":810},[],{},{"title":950},{"VI":951},"Frédéric Calon",{"url":790,"publisher":953,"properties":1002},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":954,"slug":10,"properties":955,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":958,"manageAffiliations":971,"indexDatabases":982,"url":91,"thumbnailPath":18,"statistic":997,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":956,"title":957},{"VOID":13},{"EN":15},[959,963,967],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":960,"label":961,"description":962,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":964,"label":965,"description":966,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":968,"label":969,"description":970,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[972,977],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":973,"slug":18,"properties":974,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":976,"statistic":18},[],{"title":975},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":978,"slug":18,"properties":979,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":981,"statistic":18},[],{"title":980},{"EN":52},[],[983,990],{"id":56,"indexDatabase":984,"url":69,"indexYears":18,"academicFieldIds":989,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":985,"label":986,"description":987,"key":65,"publicationTags":988,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":991,"url":84,"indexYears":85,"academicFieldIds":996,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":992,"label":993,"description":994,"key":81,"publicationTags":995,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":998,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":999,"totalCitation":102,"totalCitationByYear":1000,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":1001,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":1003,"volume":1005},{"VOID":1004},"1-1",{"VOID":458},"2023-11-01","ERROR_IN_GET_PLATFORM_ID","2026-07-20T02:00:09.288+00:00",[67,90],{"id":1011,"createTime":1012,"updateTime":1013,"relativeEntities":1014,"slug":1015,"properties":1016,"entityType":128,"verifyStatus":129,"verifyTime":1027,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":1028,"fullTextUrl":18,"authors":1029,"publicationType":403,"publisherRelationship":1322,"citationCount":1377,"citationInfo":1378,"publishDate":1387,"publishYear":1379,"citationAnalyzeStatus":17,"lastCitationAnalyze":1388,"indexDatabases":1389,"openAccess":18,"references":18,"isForceReanalyzing":462},"d44b4a9f-8988-4a31-80c3-9ea21919a364","2023-12-23T04:41:27.887+00:00","2026-07-20T01:09:33.566+00:00",[],"Increased-plasma-neurofilament-light-chain-concentration-correlates-with-severity-of-post-mortem-neurofibrillary-tangle-pathology-and-neurodegeneration",{"abstract":1017,"title":1019,"gsPaper":1021,"references":1023,"doi":1025},{"EN":1018},"Alzheimer’s disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n = 12) and AD participants (n = 57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (Aβ1–42, Aβ1–40, tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain.",{"EN":1020},"Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration",{"VOID":1022},"[\"5546903480356682118\"]",{"VOID":1024},"Bacioglu M, Maia LF, Preische O, Schelle J, Apel A, Kaeser SA, Schweighauser M, Eninger T, Lambert M, Pilotto A et al (2016) Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases. Neuron 91:56–66. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.neuron.2016.05.018\nBuerger K, Alafuzoff I, Ewers M, Pirttila T, Zinkowski R, Hampel H (2007) No correlation between CSF tau protein phosphorylated at threonine 181 with neocortical neurofibrillary pathology in Alzheimer's disease. Brain 130:e82. https:\u002F\u002Fdoi.org\u002F10.1093\u002Fbrain\u002Fawm140\nBuerger K, Ewers M, Pirttila T, Zinkowski R, Alafuzoff I, Teipel SJ, DeBernardis J, Kerkman D, McCulloch C, Soininen H et al (2006) CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain 129:3035–3041. https:\u002F\u002Fdoi.org\u002F10.1093\u002Fbrain\u002Fawl269\nByrne LM, Rodrigues FB, Blennow K, Durr A, Leavitt BR, Roos RAC, Scahill RI, Tabrizi SJ, Zetterberg H, Langbehn D et al (2017) Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. Lancet Neurol 16:601–609. https:\u002F\u002Fdoi.org\u002F10.1016\u002FS1474-4422(17)30124-2\nChatterjee P, Goozee K, Sohrabi HR, Shen K, Shah T, Asih PR, Dave P, ManYan C, Taddei K, Chung R et al (2018) Association of plasma neurofilament light chain with neocortical amyloid-beta load and cognitive performance in cognitively normal elderly participants. J Alzheimers Dis 63:479–487. https:\u002F\u002Fdoi.org\u002F10.3233\u002FJAD-180025\nDelbeuck X, Van der Linden M, Collette F (2003) Alzheimer’s disease as a disconnection syndrome? Neuropsychol Rev 13:79–92\nDisanto G, Barro C, Benkert P, Naegelin Y, Schadelin S, Giardiello A, Zecca C, Blennow K, Zetterberg H, Leppert D et al (2017) Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol 81:857–870. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fana.24954\nEngelborghs S, Sleegers K, Cras P, Brouwers N, Serneels S, De Leenheir E, Martin JJ, Vanmechelen E, Van Broeckhoven C, De Deyn PP (2007) No association of CSF biomarkers with APOEepsilon4, plaque and tangle burden in definite Alzheimer’s disease. Brain 130:2320–2326. https:\u002F\u002Fdoi.org\u002F10.1093\u002Fbrain\u002Fawm136\nGaiottino J, Norgren N, Dobson R, Topping J, Nissim A, Malaspina A, Bestwick JP, Monsch AU, Regeniter A, Lindberg RL et al (2013) Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS One 8:e75091. https:\u002F\u002Fdoi.org\u002F10.1371\u002Fjournal.pone.0075091\nGisslen M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L, Fuchs D, Spudich S, Blennow K, Zetterberg H (2016) Plasma concentration of the Neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine 3:135–140. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.ebiom.2015.11.036\nHansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, Norgren N, Linder J, Forsgren L, Constantinescu R et al (2017) Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder. Neurology 88:930–937. https:\u002F\u002Fdoi.org\u002F10.1212\u002FWNL.0000000000003680\nHerrmann N, Gauthier S, Lysy PG (2007) Clinical practice guidelines for severe Alzheimer's disease. Alzheimers Dement 3:385–397. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.jalz.2007.07.007\nHye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL, Hooper C, Rijsdijk F, Tabrizi SJ, Banner S et al (2006) Proteome-based plasma biomarkers for Alzheimer’s disease. Brain 129:3042–3050. https:\u002F\u002Fdoi.org\u002F10.1093\u002Fbrain\u002Fawl279\nHye A, Riddoch-Contreras J, Baird AL, Ashton NJ, Bazenet C, Leung R, Westman E, Simmons A, Dobson R, Sattlecker M et al (2014) Plasma proteins predict conversion to dementia from prodromal disease. Alzheimers Dement 10:799–807 e792. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.jalz.2014.05.1749\nIdland AV, Wyller TB, Stoen R, Dahl GT, Frihagen F, Braekhus A, Hassel B, Watne LO (2017) Cerebrospinal fluid phosphate in delirium after hip fracture. Dement Geriatr Cogn Dis Extra 7:309–317. https:\u002F\u002Fdoi.org\u002F10.1159\u002F000478723\nJames BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA (2016) TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia. Brain 139:2983–2993. https:\u002F\u002Fdoi.org\u002F10.1093\u002Fbrain\u002Faww224\nJanelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A, Song L, Hanlon D, Tan Hehir CA, Baker D et al (2016) Plasma beta-amyloid in Alzheimer’s disease and vascular disease. Sci Rep 6:26801. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fsrep26801\nLewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P, Maler JM, Kornhuber J, Blennow K, Zetterberg H (2018) Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimers Res Ther 10:71. https:\u002F\u002Fdoi.org\u002F10.1186\u002Fs13195-018-0404-9\nLewczuk P, Riederer P, O'Bryant SE, Verbeek MM, Dubois B, Visser PJ, Jellinger KA, Engelborghs S, Ramirez A, Parnetti L et al (2018) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the consensus of the task force on biological markers in psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry 19:244–328. https:\u002F\u002Fdoi.org\u002F10.1080\u002F15622975.2017.1375556\nMattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer's Disease Neuroimaging I (2017) Association of Plasma Neurofilament Light with Neurodegeneration in patients with Alzheimer Disease. JAMA Neurol 74:557–566. https:\u002F\u002Fdoi.org\u002F10.1001\u002Fjamaneurol.2016.6117\nMattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E, Palmqvist S, Baker D, Tan Hehir CA, Jeromin A et al (2016) Plasma tau in Alzheimer disease. Neurology 87:1827–1835. https:\u002F\u002Fdoi.org\u002F10.1212\u002FWNL.0000000000003246\nMielke MM, Hagen CE, Wennberg AMV, Airey DC, Savica R, Knopman DS, Machulda MM, Roberts RO, Jack CR Jr, Petersen RC et al (2017) Association of plasma total tau level with cognitive decline and risk of mild cognitive impairment or dementia in the mayo clinic study on aging. JAMA Neurol 74:1073–1080. https:\u002F\u002Fdoi.org\u002F10.1001\u002Fjamaneurol.2017.1359\nNakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Dore V, Fowler C, Li QX, Martins R, Rowe C et al (2018) High performance plasma amyloid-beta biomarkers for Alzheimer’s disease. Nature 554:249–254. https:\u002F\u002Fdoi.org\u002F10.1038\u002Fnature25456\nNovakova L, Zetterberg H, Sundstrom P, Axelsson M, Khademi M, Gunnarsson M, Malmestrom C, Svenningsson A, Olsson T, Piehl F et al (2017) Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology 89:2230–2237. https:\u002F\u002Fdoi.org\u002F10.1212\u002FWNL.0000000000004683\nReiber H (1994) Flow rate of cerebrospinal fluid (CSF)--a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 122:189–203\nRohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, Toombs J, Druyeh R, Cardoso MJ, Ourselin S et al (2016) Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology 87:1329–1336. https:\u002F\u002Fdoi.org\u002F10.1212\u002FWNL.0000000000003154\nSato C, Barthelemy NR, Mawuenyega KG, Patterson BW, Gordon BA, Jockel-Balsarotti J, Sullivan M, Crisp MJ, Kasten T, Kirmess KM et al (2018) Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 97:1284–1298 e1287. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.neuron.2018.02.015\nSchneider JA, Arvanitakis Z, Bang W, Bennett DA (2007) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69:2197–2204. https:\u002F\u002Fdoi.org\u002F10.1212\u002F01.wnl.0000271090.28148.24\nSeppala TT, Nerg O, Koivisto AM, Rummukainen J, Puli L, Zetterberg H, Pyykko OT, Helisalmi S, Alafuzoff I, Hiltunen M et al (2012) CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology 78:1568–1575. https:\u002F\u002Fdoi.org\u002F10.1212\u002FWNL.0b013e3182563bd0\nSjogren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K, Rosengren L, Blennow K, Wallin A (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66:510–516. https:\u002F\u002Fdoi.org\u002F10.1002\u002Fjnr.1242\nSjogren M, Rosengren L, Minthon L, Davidsson P, Blennow K, Wallin A (2000) Cytoskeleton proteins in CSF distinguish frontotemporal dementia from AD. Neurology 54:1960–1964\nSkogseth R, Hortobagyi T, Soennesyn H, Chwiszczuk L, Ffytche D, Rongve A, Ballard C, Aarsland D (2017) Accuracy of clinical diagnosis of dementia with Lewy bodies versus neuropathology. J Alzheimers Dis 59:1139–1152. https:\u002F\u002Fdoi.org\u002F10.3233\u002FJAD-170274\nSutphen CL, McCue L, Herries EM, Xiong C, Ladenson JH, Holtzman DM, Fagan AM, Adni (2018) Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer’s disease. Alzheimers Dement 14:869–879. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.jalz.2018.01.012\nTrojanowski JQ, Walkenstein N, Lee VM (1986) Expression of neurofilament subunits in neurons of the central and peripheral nervous system: an immunohistochemical study with monoclonal antibodies. J Neurosci 6:650–660\nVellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF et al (2005) Consensus statement on dementia of Alzheimer type in the severe stage. J Nutr Health Aging 9:330–338\nYilmaz A, Blennow K, Hagberg L, Nilsson S, Price RW, Schouten J, Spudich S, Underwood J, Zetterberg H, Gisslen M (2017) Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls. Expert Rev Mol Diagn 17:761–770. https:\u002F\u002Fdoi.org\u002F10.1080\u002F14737159.2017.1341313\nYuan A, Rao MV, Veeranna, Nixon RA (2017) Neurofilaments and Neurofilament proteins in health and Disease. Cold Spring Harb Perspect Biol 9. https:\u002F\u002Fdoi.org\u002F10.1101\u002Fcshperspect.a018309\nZetterberg H (2015) Plasma amyloid beta-quo vadis? Neurobiol Aging 36:2671–2673. https:\u002F\u002Fdoi.org\u002F10.1016\u002Fj.neurobiolaging.2015.07.021\nZetterberg H, Blennow K (2018) From cerebrospinal fluid to blood: the third wave of fluid biomarkers for Alzheimer's Disease. J Alzheimers Dis 64:S271–S279. https:\u002F\u002Fdoi.org\u002F10.3233\u002FJAD-179926\nZetterberg H, Skillback T, Mattsson N, Trojanowski JQ, Portelius E, Shaw LM, Weiner MW, Blennow K, Alzheimer's Disease Neuroimaging I (2016) Association of Cerebrospinal Fluid Neurofilament Light Concentration with Alzheimer Disease Progression. JAMA Neurol 73:60–67. https:\u002F\u002Fdoi.org\u002F10.1001\u002Fjamaneurol.2015.3037\nZetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, Hansson O (2013) Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther 5:9. https:\u002F\u002Fdoi.org\u002F10.1186\u002Falzrt163",{"VOID":1026},"10.1186\u002Fs40478-018-0649-3","2024-05-12T11:45:03.042+00:00","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-018-0649-3",[1030,1071,1091,1111,1131,1153,1166,1195,1210,1241,1263,1301],{"id":1031,"sortIndex":19,"researcher":18,"roles":1032,"affiliations":1033,"properties":1066,"displayName":1068,"givenName":18,"familyName":18},"6386185c-f06c-4880-846d-41e3051ee4d0",[139],[1034,1042,1050,1058],{"id":1035,"sortIndex":19,"affiliation":1036,"properties":18},"c127eebc-e3ea-4707-815b-87b44bf31b9d",{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1037,"slug":18,"properties":1038,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1041,"statistic":18},[],{"title":1039},{"VI":1040},"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden",[],{"id":1043,"sortIndex":94,"affiliation":1044,"properties":18},"a2161f89-751b-43e7-a8a7-893cc8176770",{"id":1043,"createTime":18,"updateTime":18,"relativeEntities":1045,"slug":18,"properties":1046,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1049,"statistic":18},[],{"title":1047},{"VI":1048},"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden",[],{"id":1051,"sortIndex":96,"affiliation":1052,"properties":18},"46bc8b0a-52d4-4c92-982f-d7670164a5e5",{"id":1051,"createTime":18,"updateTime":18,"relativeEntities":1053,"slug":18,"properties":1054,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1057,"statistic":18},[],{"title":1055},{"VI":1056},"King’s College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK",[],{"id":1059,"sortIndex":101,"affiliation":1060,"properties":18},"0b70f1a0-6780-4052-aa59-0e47e23b7e01",{"id":1059,"createTime":18,"updateTime":18,"relativeEntities":1061,"slug":18,"properties":1062,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1065,"statistic":18},[],{"title":1063},{"VI":1064},"NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK",[],{"title":1067,"gsAuthor":1069},{"VI":1068},"Nicholas J. Ashton",{"VOID":1070},"[\"yn-NAIAAAAAJ\"]",{"id":1072,"sortIndex":94,"researcher":18,"roles":1073,"affiliations":1074,"properties":1088,"displayName":1090,"givenName":18,"familyName":18},"72fe2070-40bb-405d-9cfb-dc9210c8623d",[139],[1075,1081],{"id":1035,"sortIndex":19,"affiliation":1076,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1077,"slug":18,"properties":1078,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1080,"statistic":18},[],{"title":1079},{"VI":1040},[],{"id":1043,"sortIndex":94,"affiliation":1082,"properties":1087},{"id":1043,"createTime":18,"updateTime":18,"relativeEntities":1083,"slug":18,"properties":1084,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1086,"statistic":18},[],{"title":1085},{"VI":1048},[],{},{"title":1089},{"VI":1090},"Antoine Leuzy",{"id":1092,"sortIndex":96,"researcher":18,"roles":1093,"affiliations":1094,"properties":1108,"displayName":1110,"givenName":18,"familyName":18},"6b2e88fc-77b3-4b4c-9e7f-a4e72e4dba29",[139],[1095,1101],{"id":1051,"sortIndex":19,"affiliation":1096,"properties":18},{"id":1051,"createTime":18,"updateTime":18,"relativeEntities":1097,"slug":18,"properties":1098,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1100,"statistic":18},[],{"title":1099},{"VI":1056},[],{"id":1059,"sortIndex":94,"affiliation":1102,"properties":1107},{"id":1059,"createTime":18,"updateTime":18,"relativeEntities":1103,"slug":18,"properties":1104,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1106,"statistic":18},[],{"title":1105},{"VI":1064},[],{},{"title":1109},{"VI":1110},"Yau Mun Lim",{"id":1112,"sortIndex":101,"researcher":18,"roles":1113,"affiliations":1114,"properties":1128,"displayName":1130,"givenName":18,"familyName":18},"aca6aeb3-543c-48d4-bb15-5bf3cbcc56ad",[139],[1115,1121],{"id":1051,"sortIndex":19,"affiliation":1116,"properties":18},{"id":1051,"createTime":18,"updateTime":18,"relativeEntities":1117,"slug":18,"properties":1118,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1120,"statistic":18},[],{"title":1119},{"VI":1056},[],{"id":1059,"sortIndex":94,"affiliation":1122,"properties":1127},{"id":1059,"createTime":18,"updateTime":18,"relativeEntities":1123,"slug":18,"properties":1124,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1126,"statistic":18},[],{"title":1125},{"VI":1064},[],{},{"title":1129},{"VI":1130},"Claire Troakes",{"id":1132,"sortIndex":100,"researcher":18,"roles":1133,"affiliations":1134,"properties":1150,"displayName":1152,"givenName":18,"familyName":18},"03093efd-3818-42fa-8b1e-9c4f321725e0",[139],[1135,1141],{"id":1051,"sortIndex":19,"affiliation":1136,"properties":18},{"id":1051,"createTime":18,"updateTime":18,"relativeEntities":1137,"slug":18,"properties":1138,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1140,"statistic":18},[],{"title":1139},{"VI":1056},[],{"id":1142,"sortIndex":94,"affiliation":1143,"properties":1149},"46e40563-060c-4618-a242-a0cb09de33a2",{"id":1142,"createTime":18,"updateTime":18,"relativeEntities":1144,"slug":18,"properties":1145,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1148,"statistic":18},[],{"title":1146},{"VI":1147},"MTA-DE Cerebrovascular and Neurodegenerative Research Group, Department of Neurology, University of Debrecen, Debrecen, Hungary",[],{},{"title":1151},{"VI":1152},"Tibor Hortobágyi",{"id":1154,"sortIndex":99,"researcher":18,"roles":1155,"affiliations":1156,"properties":1163,"displayName":1165,"givenName":18,"familyName":18},"e9beba8e-adb3-4ed8-a9fe-6bd19302276a",[139],[1157],{"id":1035,"sortIndex":19,"affiliation":1158,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1159,"slug":18,"properties":1160,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1162,"statistic":18},[],{"title":1161},{"VI":1040},[],{"title":1164},{"VI":1165},"Kina Höglund",{"id":1167,"sortIndex":285,"researcher":18,"roles":1168,"affiliations":1169,"properties":1192,"displayName":1194,"givenName":18,"familyName":18},"2b0475da-56dc-4086-99de-23a93ef6f3f0",[139],[1170,1176,1183],{"id":1051,"sortIndex":19,"affiliation":1171,"properties":18},{"id":1051,"createTime":18,"updateTime":18,"relativeEntities":1172,"slug":18,"properties":1173,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1175,"statistic":18},[],{"title":1174},{"VI":1056},[],{"id":1059,"sortIndex":94,"affiliation":1177,"properties":1182},{"id":1059,"createTime":18,"updateTime":18,"relativeEntities":1178,"slug":18,"properties":1179,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1181,"statistic":18},[],{"title":1180},{"VI":1064},[],{},{"id":1184,"sortIndex":96,"affiliation":1185,"properties":1191},"6f4690a6-337b-4a6d-86a4-2123dbd77d4d",{"id":1184,"createTime":18,"updateTime":18,"relativeEntities":1186,"slug":18,"properties":1187,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1190,"statistic":18},[],{"title":1188},{"VI":1189},"Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway",[],{},{"title":1193},{"VI":1194},"Dag Aarsland",{"id":1196,"sortIndex":308,"researcher":18,"roles":1197,"affiliations":1198,"properties":1207,"displayName":1209,"givenName":18,"familyName":18},"f898bbcf-cb73-4319-99a2-c7367d928e65",[139],[1199],{"id":1200,"sortIndex":19,"affiliation":1201,"properties":18},"3b17e6b5-c9c5-43ec-8534-26d10a4c96dd",{"id":1200,"createTime":18,"updateTime":18,"relativeEntities":1202,"slug":18,"properties":1203,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1206,"statistic":18},[],{"title":1204},{"VI":1205},"Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK",[],{"title":1208},{"VI":1209},"Simon Lovestone",{"id":1211,"sortIndex":333,"researcher":18,"roles":1212,"affiliations":1213,"properties":1238,"displayName":1240,"givenName":18,"familyName":18},"14172a3a-e3db-4ee5-acf7-3c588a192dd5",[139],[1214,1220,1229],{"id":1035,"sortIndex":19,"affiliation":1215,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1216,"slug":18,"properties":1217,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1219,"statistic":18},[],{"title":1218},{"VI":1040},[],{"id":1221,"sortIndex":94,"affiliation":1222,"properties":1228},"490f13a2-5b64-4517-a054-b127730debd3",{"id":1221,"createTime":18,"updateTime":18,"relativeEntities":1223,"slug":18,"properties":1224,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1227,"statistic":18},[],{"title":1225},{"VI":1226},"Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden",[],{},{"id":1230,"sortIndex":96,"affiliation":1231,"properties":1237},"7ec0a5f7-3eb7-48e3-8350-94fd6bdf41ec",{"id":1230,"createTime":18,"updateTime":18,"relativeEntities":1232,"slug":18,"properties":1233,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1236,"statistic":18},[],{"title":1234},{"VI":1235},"Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK",[],{},{"title":1239},{"VI":1240},"Michael Schöll",{"id":1242,"sortIndex":354,"researcher":18,"roles":1243,"affiliations":1244,"properties":1260,"displayName":1262,"givenName":18,"familyName":18},"3b4e3559-b224-4ba7-85ef-35af910320d6",[139],[1245,1251],{"id":1035,"sortIndex":19,"affiliation":1246,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1247,"slug":18,"properties":1248,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1250,"statistic":18},[],{"title":1249},{"VI":1040},[],{"id":1252,"sortIndex":94,"affiliation":1253,"properties":1259},"196fe59f-81b5-4f62-bd27-69c0192e35f2",{"id":1252,"createTime":18,"updateTime":18,"relativeEntities":1254,"slug":18,"properties":1255,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1258,"statistic":18},[],{"title":1256},{"VI":1257},"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden",[],{},{"title":1261},{"VI":1262},"Kaj Blennow",{"id":1264,"sortIndex":375,"researcher":18,"roles":1265,"affiliations":1266,"properties":1298,"displayName":1300,"givenName":18,"familyName":18},"c84ee557-96b5-4dd2-ba96-6003dbefc05a",[139],[1267,1273,1280,1289],{"id":1035,"sortIndex":19,"affiliation":1268,"properties":18},{"id":1035,"createTime":18,"updateTime":18,"relativeEntities":1269,"slug":18,"properties":1270,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1272,"statistic":18},[],{"title":1271},{"VI":1040},[],{"id":1252,"sortIndex":94,"affiliation":1274,"properties":1279},{"id":1252,"createTime":18,"updateTime":18,"relativeEntities":1275,"slug":18,"properties":1276,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1278,"statistic":18},[],{"title":1277},{"VI":1257},[],{},{"id":1281,"sortIndex":96,"affiliation":1282,"properties":1288},"d4ed2936-ff73-4b23-8927-27a58ccbd124",{"id":1281,"createTime":18,"updateTime":18,"relativeEntities":1283,"slug":18,"properties":1284,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1287,"statistic":18},[],{"title":1285},{"VI":1286},"Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, UK",[],{},{"id":1290,"sortIndex":101,"affiliation":1291,"properties":1297},"7e6167f0-9fdf-4d9c-ab74-c3014e1798cd",{"id":1290,"createTime":18,"updateTime":18,"relativeEntities":1292,"slug":18,"properties":1293,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1296,"statistic":18},[],{"title":1294},{"VI":1295},"UK Dementia Research Institute at UCL, London, UK",[],{},{"title":1299},{"VI":1300},"Henrik Zetterberg",{"id":1302,"sortIndex":1303,"researcher":18,"roles":1304,"affiliations":1305,"properties":1319,"displayName":1321,"givenName":18,"familyName":18},"6eae1aa1-3b7b-437c-b60f-650f617fc182",11,[139],[1306,1312],{"id":1051,"sortIndex":19,"affiliation":1307,"properties":18},{"id":1051,"createTime":18,"updateTime":18,"relativeEntities":1308,"slug":18,"properties":1309,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1311,"statistic":18},[],{"title":1310},{"VI":1056},[],{"id":1059,"sortIndex":94,"affiliation":1313,"properties":1318},{"id":1059,"createTime":18,"updateTime":18,"relativeEntities":1314,"slug":18,"properties":1315,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1317,"statistic":18},[],{"title":1316},{"VI":1064},[],{},{"title":1320},{"VI":1321},"Abdul Hye",{"url":1028,"publisher":1323,"properties":1372},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1324,"slug":10,"properties":1325,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1328,"manageAffiliations":1341,"indexDatabases":1352,"url":91,"thumbnailPath":18,"statistic":1367,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":1326,"title":1327},{"VOID":13},{"EN":15},[1329,1333,1337],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1330,"label":1331,"description":1332,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":1334,"label":1335,"description":1336,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":1338,"label":1339,"description":1340,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[1342,1347],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":1343,"slug":18,"properties":1344,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1346,"statistic":18},[],{"title":1345},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":1348,"slug":18,"properties":1349,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1351,"statistic":18},[],{"title":1350},{"EN":52},[],[1353,1360],{"id":56,"indexDatabase":1354,"url":69,"indexYears":18,"academicFieldIds":1359,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":1355,"label":1356,"description":1357,"key":65,"publicationTags":1358,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":1361,"url":84,"indexYears":85,"academicFieldIds":1366,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":1362,"label":1363,"description":1364,"key":81,"publicationTags":1365,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":1368,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":1369,"totalCitation":102,"totalCitationByYear":1370,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":1371,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":1373,"volume":1375},{"VOID":1374},"1-11",{"VOID":1376},"7",190,{"total":1377,"publishYear":1379,"statisticByYear":1380},2019,{"2019":1381,"2020":1382,"2021":1382,"2022":1383,"2023":1384,"2024":1385,"2025":1386,"2026":94},15,40,21,28,30,14,"2019-01-09","2026-07-20T01:09:33.565+00:00",[67,90],{"id":1391,"createTime":1392,"updateTime":1393,"relativeEntities":1394,"slug":1395,"properties":1396,"entityType":128,"verifyStatus":129,"verifyTime":1407,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":1408,"fullTextUrl":18,"authors":1409,"publicationType":403,"publisherRelationship":1560,"citationCount":19,"citationInfo":1614,"publishDate":1616,"publishYear":460,"citationAnalyzeStatus":661,"lastCitationAnalyze":1617,"indexDatabases":1618,"openAccess":18,"references":18,"isForceReanalyzing":462},"bb93a292-5a67-4f86-8132-3f68aa528273","2023-12-13T18:36:45.364+00:00","2026-07-18T14:07:36.261+00:00",[],"Exceptionally-rare-IDH1-mutant-adult-medulloblastoma-with-concurrent-GNAS-mutation-revealed-by-in-vivo-magnetic-resonance-spectroscopy-and-deep-sequencing",{"abstract":1397,"title":1399,"gsPaper":1401,"references":1403,"doi":1405},{"EN":1398},"Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adults. Based on transcriptome profile, MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) mutations have been described in several tumors, including gliomas, while in MB are rarely reported and not routinely investigated. By means of magnetic resonance spectroscopy (MRS), we unequivocally assessed the presence the oncometabolite D-2-hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutations, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also rarely described in MB. To the best of our knowledge, this is the first reported case of MB simultaneously harboring both mutations. Of note, tumor exhibited a heterogeneous phenotype with a tumor component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting co-existence of two different major tumor subclones. These findings drew attention to the need for a deeper genetic characterization of MB, in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, our results underlined the importance of performing MRS for the identification of IDH mutations in non-glial tumors. The use of throughput molecular profiling analysis and advanced medical imaging will certainly increase the frequency with which tumor entities with rare molecular alterations will be identified. Whether these findings have any specific therapeutic implications or prognostic relevance requires further investigations.",{"EN":1400},"Exceptionally rare IDH1-mutant adult medulloblastoma with concurrent GNAS mutation revealed by in vivo magnetic resonance spectroscopy and deep sequencing",{"VOID":1402},"[\"9203017386641306501\"]",{"VOID":1404},"Andronesi OC, Kim GS, Gerstner E, Batchelor T, Tzika AA, Fantin VR et al (2012) Detection of 2-hydroxyglutarate in IDH-mutated glioma patients by in vivo spectral-editing and 2D correlation magnetic resonance spectroscopy. Sci Transl Med 4(116):116ra4\nBennett CD, Kohe SE, Gill SK, Davies NP, Wilson M, Storer LCD et al (2018) Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours. Sci Rep 10(1):11992\nBlüml S, Margol AS, Sposto R, Kennedy RJ, Robison NJ, Vali M et al (2016) Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy. Neurooncology 18(1):126–131\nBranzoli F, Di Stefano AL, Capelle L, Ottolenghi C, Valabrègue R, Deelchand DK et al (2018) Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy. Neurooncology 20:907–916\nCapper D, Jones DTW, Sill M, Hovestadt V, Schrimpf D, Sturm D et al (2018) DNA methylation-based classification of central nervous system tumours. Nature 555:469–474\nChoi C, Ganji SK, De Berardinis RJ, Hatanpaa KJ, Rakheja D, Kovacs Z et al (2012) 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med 18:624–629\nChoi C, Raisanen JM, Ganji SK, Zhang S, McNeil SS, An Z et al (2016) Prospective longitudinal analysis of 2-Hydroxyglutarate magnetic resonance spectroscopy identifies broad clinical utility for the management of patients with IDH-Mutant glioma. J Clin Oncol 34:4030–4039\nColicelli J (2004) Human RAS superfamily proteins and related GTPases. Sci STKE 7(250):RE13\nColtin H, Sundaresan L, Smith KS, Skowron P, Massimi L, Eberhart CG et al (2021) Subgroup and subtype-specific outcomes in adult medulloblastoma. Acta Neuropathol 142:859–871\nCorno D, Pala M, Cominelli M, Cipelletti B, Leto K, Croci L et al (2012) Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification. Cancer Discov 2:554–568\nDi Ieva A, Magnussen JS, McIntosh J, Mulcahy MJ, Pardey M, Choi C (2020) Magnetic resonance Spectroscopic Assessment of Isocitrate Dehydrogenase Status in Gliomas: the New Frontiers of Spectrobiopsy in Neurodiagnostics. World Neurosurg 133:e421–e427\nEl-Ayadi M, Egervari K, Merkler D, McKee TA, Gumy-Pause F, Stichel D et al (2018) Concurrent IDH1 and SMARCB1 mutations in Pediatric Medulloblastoma: a Case Report. Front Neurol 9:398\nHe X, Zhang L, Chen Y, Remke M, Shih D, Lu F et al (2014) The G protein α subunit Gαs is a tumor suppressor in sonic hedgehog-driven medulloblastoma. Nat Med 20(9):1035–4220\nJaunmuktane Z, Capper D, Jones DTW, Schrimpf D, Sill M, Dutt M et al (2019) Methylation array profiling of adult brain tumours: diagnostic outcomes in a large, single centre. Acta Neuropathol Commun 20(1):247\nKaur K, Kakkar A, Kumar A, Mallick S, Julka PK, Gupta D et al (2016) Integrating Molecular Subclassification of Medulloblastomas into Routine Clinical Practice: A Simplified Approach. Brain Pathol 26:334–343\nLeather T, Jenkinson MD, Das K, Poptani H (2017) Magnetic resonance spectroscopy for detection of 2-Hydroxyglutarate as a biomarker for IDH Mutation in Gliomas. Metabolites 19(2):29\nLouis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D et al (2021) The 2021 WHO classification of tumors of the central nervous System: a summary. Neuro Oncol 23(8):1231–1251\nMajd N, Penas-Prado M (2019) Updates on management of adult Medulloblastoma. Nat Rev Cancer 20:64\nNatsumeda M, Igarashi H (2021) Detection of 2-Hydroxyglutarate by 3.0-Tesla magnetic resonance spectroscopy in gliomas with rare IDH mutations: making sense of “False-Positive”. Cases Diagnostics 16(11):2129\nNorthcott PA, Buchhalter I, Morrissy AS, Hovestadt V, Weischenfeldt J, Ehrenberger T et al (2017) The whole-genome landscape of medulloblastoma subtypes. Nature 547:311–317\nNorthcott PA, Robinson GW, Kratz CP, Mabbott DJ, Pomeroy SL, Clifford SC et al (2019) Medulloblastoma. Nat Reviews Disease Primers 5:11\nPandit SB, Srinivasan N (2003) Survey for g-proteins in the prokaryotic genomes: prediction of functional roles based on classification. Proteins 52:585–597\nPanigrahy A, Krieger MD, Gonzalez-Gomez I, Liu X, McComb JG, Finlay JL et al (2006) Quantitative short echo time 1H-MR spectroscopy of untreated pediatric brain tumors: preoperative diagnosis and characterization. Am J Neuroradiol 27:560–572\nProvencher SW (1993) Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30:672–679\nPusch S, Schweizer L, Beck AC, Lehmler JM, Weissert S, Balss J et al (2014) D-2-Hydroxyglutarate producing neo-enzymatic activity inversely correlates with frequency of the type of isocitrate dehydrogenase 1 mutations found in glioma. Acta Neuropathol Commun 2:19\nShihab HA, Gough J, Cooper DN, Day IN, Gaunt TR (2013) Predicting the functional consequences of cancer-associated amino acid substitutions. Bioinformatics 29:1504–1510\nSnuderl M, Triscott J, Northcott PA, Shih HA, Kong E, Robinson H et al (2015) Deep sequencing identifies IDH1 R132S mutation in adult medulloblastoma. J Clin Oncol 33:e27–31\nSunahara RK, Tesmer JJ, Gilman AG, Sprang SR (1997) Crystal structure of the adenylyl cyclase activator Gsalpha. Science 278:1943–1947\nTaylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC et al (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465–472\nTesileanu CMS, Vallentgoed WR, Sanson M, Taal W, Clement PM, Wick W et al (2021) Non-IDH1-R132H IDH1\u002F2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations. Acta Neuropathol 141(6):945–957\nTokita MJ, Nahas S, Briggs B, Malicki DM, Mesirov JP, Reyes IAC et al (2019) Biallelic loss of GNAS in a patient with pediatric medulloblastoma. Cold Spring Harb Mol Case Stud 23(5):a004572",{"VOID":1406},"10.1186\u002Fs40478-023-01531-y","2024-06-23T15:45:36.803+00:00","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-023-01531-y",[1410,1425,1450,1467,1480,1493,1508,1523,1547],{"id":1411,"sortIndex":19,"researcher":18,"roles":1412,"affiliations":1413,"properties":1422,"displayName":1424,"givenName":18,"familyName":18},"60fd180c-2d01-4dfe-b483-6dcbeae896c7",[139],[1414],{"id":1415,"sortIndex":19,"affiliation":1416,"properties":18},"429da320-773d-4537-b2ab-2cb07756a943",{"id":1415,"createTime":18,"updateTime":18,"relativeEntities":1417,"slug":18,"properties":1418,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1421,"statistic":18},[],{"title":1419},{"VI":1420},"Department of Radiology, Neuroradiology Unit, ASST Spedali Civili University Hospital, Brescia, Italy",[],{"title":1423},{"VI":1424},"Roberto Liserre",{"id":1426,"sortIndex":94,"researcher":18,"roles":1427,"affiliations":1428,"properties":1445,"displayName":1447,"givenName":18,"familyName":18},"7fbd0c88-a420-4007-a2f9-0250f18f5fe4",[139],[1429,1437],{"id":1430,"sortIndex":19,"affiliation":1431,"properties":18},"ba9a4bd2-cfcc-4459-8601-7f510557642c",{"id":1430,"createTime":18,"updateTime":18,"relativeEntities":1432,"slug":18,"properties":1433,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1436,"statistic":18},[],{"title":1434},{"VI":1435},"Paris Brain Institute - Institut du Cerveau (ICM), Centre de NeuroImagerie de Recherche (CENIR), Paris, France",[],{"id":1438,"sortIndex":94,"affiliation":1439,"properties":18},"3bdf561b-d4a9-4e95-9a29-35ac6cae2354",{"id":1438,"createTime":18,"updateTime":18,"relativeEntities":1440,"slug":18,"properties":1441,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1444,"statistic":18},[],{"title":1442},{"VI":1443},"Sorbonne Université, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France",[],{"title":1446,"gsAuthor":1448},{"VI":1447},"Francesca Branzoli",{"VOID":1449},"[\"OjHLc44AAAAJ\"]",{"id":1451,"sortIndex":96,"researcher":18,"roles":1452,"affiliations":1453,"properties":1462,"displayName":1464,"givenName":18,"familyName":18},"ebd6f158-76be-4a78-9496-a5c65e8aeeda",[139],[1454],{"id":1455,"sortIndex":19,"affiliation":1456,"properties":18},"ae60283a-9538-493e-a332-2d8b4434c818",{"id":1455,"createTime":18,"updateTime":18,"relativeEntities":1457,"slug":18,"properties":1458,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1461,"statistic":18},[],{"title":1459},{"VI":1460},"Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy",[],{"title":1463,"gsAuthor":1465},{"VI":1464},"Francesca Pagani",{"VOID":1466},"[\"EKDmZi4AAAAJ\"]",{"id":1468,"sortIndex":101,"researcher":18,"roles":1469,"affiliations":1470,"properties":1477,"displayName":1479,"givenName":18,"familyName":18},"b8590ecb-6449-4a6d-bbf3-653818469c77",[139],[1471],{"id":1455,"sortIndex":19,"affiliation":1472,"properties":18},{"id":1455,"createTime":18,"updateTime":18,"relativeEntities":1473,"slug":18,"properties":1474,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1476,"statistic":18},[],{"title":1475},{"VI":1460},[],{"title":1478},{"VI":1479},"Magdalena Gryzik",{"id":1481,"sortIndex":100,"researcher":18,"roles":1482,"affiliations":1483,"properties":1490,"displayName":1492,"givenName":18,"familyName":18},"6d2a6ea2-ef7b-4709-be33-3ddf797352ab",[139],[1484],{"id":1455,"sortIndex":19,"affiliation":1485,"properties":18},{"id":1455,"createTime":18,"updateTime":18,"relativeEntities":1486,"slug":18,"properties":1487,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1489,"statistic":18},[],{"title":1488},{"VI":1460},[],{"title":1491},{"VI":1492},"Manuela Cominelli",{"id":1494,"sortIndex":99,"researcher":18,"roles":1495,"affiliations":1496,"properties":1505,"displayName":1507,"givenName":18,"familyName":18},"b134abb6-76ca-410c-b8d4-1c6b3ff90904",[139],[1497],{"id":1498,"sortIndex":19,"affiliation":1499,"properties":18},"bd4d884d-ecc8-441e-bef5-3dc7238eb511",{"id":1498,"createTime":18,"updateTime":18,"relativeEntities":1500,"slug":18,"properties":1501,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1504,"statistic":18},[],{"title":1502},{"VI":1503},"Department of Pediatric Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy",[],{"title":1506},{"VI":1507},"Evelina Miele",{"id":1509,"sortIndex":285,"researcher":18,"roles":1510,"affiliations":1511,"properties":1520,"displayName":1522,"givenName":18,"familyName":18},"320ad939-09f0-433d-a446-3dcf35c5a263",[139],[1512],{"id":1513,"sortIndex":19,"affiliation":1514,"properties":18},"eaefc5dd-1d43-4b1d-a02a-0747337c390a",{"id":1513,"createTime":18,"updateTime":18,"relativeEntities":1515,"slug":18,"properties":1516,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1519,"statistic":18},[],{"title":1517},{"VI":1518},"Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, USA",[],{"title":1521},{"VI":1522},"Małgorzata Marjańska",{"id":1524,"sortIndex":308,"researcher":18,"roles":1525,"affiliations":1526,"properties":1544,"displayName":1546,"givenName":18,"familyName":18},"706ee737-9143-4912-8bb3-2a93b9982058",[139],[1527,1535],{"id":1528,"sortIndex":19,"affiliation":1529,"properties":18},"fdf4f1ab-136f-485e-859f-4e8631b26735",{"id":1528,"createTime":18,"updateTime":18,"relativeEntities":1530,"slug":18,"properties":1531,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1534,"statistic":18},[],{"title":1532},{"VI":1533},"Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy",[],{"id":1536,"sortIndex":94,"affiliation":1537,"properties":1543},"e15feb31-fe2c-4c8e-b2b2-b55167939abe",{"id":1536,"createTime":18,"updateTime":18,"relativeEntities":1538,"slug":18,"properties":1539,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1542,"statistic":18},[],{"title":1540},{"VI":1541},"Catholic University School of Medicine, Rome, Italy",[],{},{"title":1545},{"VI":1546},"Francesco Doglietto",{"id":1548,"sortIndex":333,"researcher":18,"roles":1549,"affiliations":1550,"properties":1557,"displayName":1559,"givenName":18,"familyName":18},"bbb76cae-9b51-4ec4-a7ea-bf02c5147efa",[139],[1551],{"id":1455,"sortIndex":19,"affiliation":1552,"properties":18},{"id":1455,"createTime":18,"updateTime":18,"relativeEntities":1553,"slug":18,"properties":1554,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1556,"statistic":18},[],{"title":1555},{"VI":1460},[],{"title":1558},{"VI":1559},"Pietro Luigi Poliani",{"url":1408,"publisher":1561,"properties":1610},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1562,"slug":10,"properties":1563,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1566,"manageAffiliations":1579,"indexDatabases":1590,"url":91,"thumbnailPath":18,"statistic":1605,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":1564,"title":1565},{"VOID":13},{"EN":15},[1567,1571,1575],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1568,"label":1569,"description":1570,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":1572,"label":1573,"description":1574,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":1576,"label":1577,"description":1578,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[1580,1585],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":1581,"slug":18,"properties":1582,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1584,"statistic":18},[],{"title":1583},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":1586,"slug":18,"properties":1587,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1589,"statistic":18},[],{"title":1588},{"EN":52},[],[1591,1598],{"id":56,"indexDatabase":1592,"url":69,"indexYears":18,"academicFieldIds":1597,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":1593,"label":1594,"description":1595,"key":65,"publicationTags":1596,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":1599,"url":84,"indexYears":85,"academicFieldIds":1604,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":1600,"label":1601,"description":1602,"key":81,"publicationTags":1603,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":1606,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":1607,"totalCitation":102,"totalCitationByYear":1608,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":1609,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":1611,"volume":1613},{"VOID":1612},"1-9",{"VOID":458},{"total":19,"publishYear":460,"statisticByYear":1615},{},"2023-03-20","2026-07-18T14:07:36.260+00:00",[67,90],{"id":1620,"createTime":1621,"updateTime":1622,"relativeEntities":1623,"slug":1624,"properties":1625,"entityType":128,"verifyStatus":129,"verifyTime":1636,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":1637,"fullTextUrl":18,"authors":1638,"publicationType":403,"publisherRelationship":1719,"citationCount":18,"citationInfo":18,"publishDate":1772,"publishYear":1773,"citationAnalyzeStatus":17,"lastCitationAnalyze":1774,"indexDatabases":1775,"openAccess":18,"references":18,"isForceReanalyzing":462},"b8cb6c20-45cd-4e7a-8125-4cd1b648fce1","2024-01-24T14:53:46.651+00:00","2026-06-19T00:56:01.380+00:00",[],"Unusual-cerebral-vascular-prion-protein-amyloid-distribution-in-scrapie-infected-transgenic-mice-expressing-anchorless-prion-protein",{"abstract":1626,"title":1628,"gsPaper":1630,"references":1632,"doi":1634},{"EN":1627},"In some prion diseases, misfolded aggregated protease-resistant prion protein (PrPres) is found in brain as amyloid, which can cause cerebral amyloid angiopathy. Small diffusible precursors of PrPres amyloid might flow with brain interstitial fluid (ISF), possibly accounting for the perivascular and intravascular distribution of PrPres amyloid. We previously reported that PrPres amyloid in scrapie-infected transgenic mice appeared to delay clearance of microinjected brain ISF tracer molecules. Here we studied distribution of PrPres amyloid on capillaries, arteries and veins to test whether vascular specificity of PrPres corresponded to distribution of ISF tracer molecules. To distinguish PrPres-positive arteries from veins and capillaries, scrapie-infected mouse brains were studied by immunodetection of alpha smooth muscle actin. ISF was studied using fluorescein-labeled ovalbumin microinjected into brain as a tracer. In infected preclinical or clinical mice, PrPres was found mostly on capillaries (73-78%). Lower levels were found on arteries (11-14%) and veins (11-13%). Compared to PrPres, ISF tracer was found at higher levels on capillaries (96-97%), and the remaining tracer was found at a skewed ratio of 4 to 1 on arteries and veins respectively. PrPres association with blood vessels suggested that ISF flow might transport diffusible PrPres precursor molecules to perivascular sites. However, the different vascular specificity of PrPres and ISF tracer indicated that ISF flow did not alone control PrPres dissemination. Possibly blood vessel basement membrane (BM) components, such as glucosaminoglycans, might concentrate small PrPres aggregates and serve as scaffolds for PrP conversion on multiple vessel types.",{"EN":1629},"Unusual cerebral vascular prion protein amyloid distribution in scrapie-infected transgenic mice expressing anchorless prion protein",{"VOID":1631},"[\"2322999614883381169\"]",{"VOID":1633},"Aguzzi A, Polymenidou M: Mammalian prion biology: one century of evolving concepts. Cell 2004,116(2):313–327. 10.1016\u002FS0092-8674(03)01031-6\nCaughey B, Baron GS, Chesebro B, Jeffrey M: Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. Annu Rev Biochem 2009, 78: 177–204. 10.1146\u002Fannurev.biochem.78.082907.145410\nBudka H, Aguzzi A, Brown P, Brucher JM, Bugiani O, Gullotta F, Haltia M, Hauw JJ, Ironside JW, Jellinger K, et al.: Neuropathological diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 1995,5(4):459–466. 10.1111\u002Fj.1750-3639.1995.tb00625.x\nGonzalez L, Martin S, Begara-McGorum I, Hunter N, Houston F, Simmons M, Jeffrey M: Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie. J Comp Pathol 2002,126(1):17–29. 10.1053\u002Fjcpa.2001.0516\nJeffrey M, Goodsir CM, Bruce ME, McBride PA, Fraser JR: In vivo toxicity of prion protein in murine scrapie: ultrastructural and immunogold studies. Neuropathol Appl Neurobiol 1997,23(2):93–101. 10.1111\u002Fj.1365-2990.1997.tb01191.x\nParchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H: Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999,46(2):224–233. 10.1002\u002F1531-8249(199908)46:2\u003C224::AID-ANA12>3.0.CO;2-W\nGhetti B, Piccardo P, Frangione B, Bugiani O, Giaccone G, Young K, Prelli F, Farlow MR, Dlouhy SR, Tagliavini F: Prion protein amyloidosis. Brain Pathol 1996,6(2):127–145. 10.1111\u002Fj.1750-3639.1996.tb00796.x\nJeffrey M, Goodsir CM, Bruce ME, McBride PA, Scott JR, Halliday WG: Infection specific prion protein (PrP) accumulates on neuronal plasmalemma in scrapie infected mice. Neurosci Lett 1992,147(1):106–109. 10.1016\u002F0304-3940(92)90785-6\nPiccardo P, Seiler C, Dlouhy SR, Young K, Farlow MR, Prelli F, Frangione B, Bugiani O, Tagliavini F, Ghetti B: Proteinase-K-resistant prion protein isoforms in Gerstmann-Straussler-Scheinker disease (Indiana kindred). J Neuropathol Exp Neurol 1996,55(11):1157–1163. 10.1097\u002F00005072-199611000-00007\nChesebro B, Race B, Meade-White K, Lacasse R, Race R, Klingeborn M, Striebel J, Dorward D, McGovern G, Jeffrey M: Fatal transmissible amyloid encephalopathy: a new type of prion disease associated with lack of prion protein membrane anchoring. PLoS Pathog 2010,6(3):e1000800. 10.1371\u002Fjournal.ppat.1000800\nRace B, Meade-White K, Oldstone MB, Race R, Chesebro B: Detection of prion infectivity in fat tissues of scrapie-infected mice. PLoS Pathog 2008,4(12):e1000232. 10.1371\u002Fjournal.ppat.1000232\nTrifilo MJ, Yajima T, Gu Y, Dalton N, Peterson KL, Race RE, Meade-White K, Portis JL, Masliah E, Knowlton KU, Chesebro B, Oldstone MB: Prion-induced amyloid heart disease with high blood infectivity in transgenic mice. Science 2006,313(5783):94–97. 10.1126\u002Fscience.1128635\nRevesz T, Holton JL, Lashley T, Plant G, Frangione B, Rostagno A, Ghiso J: Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies. Acta Neuropathol 2009,118(1):115–130. 10.1007\u002Fs00401-009-0501-8\nGhetti B, Piccardo P, Spillantini MG, Ichimiya Y, Porro M, Perini F, Kitamoto T, Tateishi J, Seiler C, Frangione B, Bugiani O, Giaccone G, Prelli F, Goedert M, Dlouhy SR, Tagliavini F: Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci USA 1996,93(2):744–748. 10.1073\u002Fpnas.93.2.744\nJansen C, Parchi P, Capellari S, Vermeij AJ, Corrado P, Baas F, Strammiello R, van Gool WA, van Swieten JC, Rozemuller AJ: Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP. Acta Neuropathol 2010,119(2):189–197. 10.1007\u002Fs00401-009-0609-x\nJayadev S, Nochlin D, Poorkaj P, Steinbart EJ, Mastrianni JA, Montine TJ, Ghetti B, Schellenberg GD, Bird TD, Leverenz JB: Familial prion disease with Alzheimer disease-like tau pathology and clinical phenotype. Ann Neurol 2011,69(4):712–720. 10.1002\u002Fana.22264\nMandybur TI: The incidence of cerebral amyloid angiopathy in Alzheimer’s disease. Neurology 1975,25(2):120–126. 10.1212\u002FWNL.25.2.120\nMorimatsu M, Hirai S, Muramatsu A, Yoshikawa M: Senile degenerative brain lesions and dementia. J Am Geriatr Soc 1975,23(9):390–406.\nThal DR, Ghebremedhin E, Rub U, Yamaguchi H, Del Tredici K, Braak H: Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2002,61(3):282–293.\nYamaguchi H, Yamazaki T, Lemere CA, Frosch MP, Selkoe DJ: Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimer’s disease. An immunoelectron microscopic study. Am J Pathol 1992,141(1):249–259.\nWeller RO, Massey A, Newman TA, Hutchings M, Kuo YM, Roher AE: Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer’s disease. Am J Pathol 1998,153(3):725–733. 10.1016\u002FS0002-9440(10)65616-7\nCarare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JA, Perry VH, Weller RO: Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Neuropathol Appl Neurobiol 2008,34(2):131–144. 10.1111\u002Fj.1365-2990.2007.00926.x\nWeller RO, Djuanda E, Yow HY, Carare RO: Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol 2009,117(1):1–14. 10.1007\u002Fs00401-008-0457-0\nWeller RO, Boche D, Nicoll JA: Microvasculature changes and cerebral amyloid angiopathy in Alzheimer’s disease and their potential impact on therapy. Acta Neuropathol 2009,118(1):87–102. 10.1007\u002Fs00401-009-0498-z\nChesebro B, Trifilo M, Race R, Meade-White K, Teng C, LaCasse R, Raymond L, Favara C, Baron G, Priola S, Caughey B, Masliah E, Oldstone M: Anchorless prion protein results in infectious amyloid disease without clinical scrapie. Science 2005,308(5727):1435–1439. 10.1126\u002Fscience.1110837\nKlingeborn M, Race B, Meade-White KD, Rosenke R, Striebel JF, Chesebro B: Crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection. J Virol 2011,85(4):1484–1494. 10.1128\u002FJVI.02167-10\nRangel A, Race B, Striebel J, Chesebro B: Non-amyloid and amyloid prion protein deposits in prion-infected mice differ in blockage of interstitial brain fluid. Neuropathol Appl Neurobiol 2013,39(3):217–230. 10.1111\u002Fj.1365-2990.2012.01303.x\nTribouillard-Tanvier D, Race B, Striebel JF, Carroll JA, Phillips K, Chesebro B: Early cytokine elevation, PrPres deposition, and gliosis in mouse scrapie: no effect on disease by deletion of cytokine genes IL-12p40 and IL-12p35. J Virol 2012,86(19):10377–10383. 10.1128\u002FJVI.01340-12\nMatsunaga Y, Peretz D, Williamson A, Burton D, Mehlhorn I, Groth D, Cohen FE, Prusiner SB, Baldwin MA: Cryptic epitopes in N-terminally truncated prion protein are exposed in the full-length molecule: dependence of conformation on pH. Proteins 2001,44(2):110–118. 10.1002\u002Fprot.1077\nHawkes CA, Hartig W, Kacza J, Schliebs R, Weller RO, Nicoll JA, Carare RO: Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol 2011,121(4):431–443. 10.1007\u002Fs00401-011-0801-7\nMisumi Y, Ando Y, Ueda M, Obayashi K, Jono H, Su Y, Yamashita T, Uchino M: Chain reaction of amyloid fibril formation with induction of basement membrane in familial amyloidotic polyneuropathy. J Pathol 2009,219(4):481–490. 10.1002\u002Fpath.2618\nCaughey B, Brown K, Raymond GJ, Katzenstein GE, Thresher W: Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and congo red [corrected]. J Virol 1994,68(4):2135–2141.\nWong C, Xiong LW, Horiuchi M, Raymond L, Wehrly K, Chesebro B, Caughey B: Sulfated glycans and elevated temperature stimulate PrP(Sc)-dependent cell-free formation of protease-resistant prion protein. EMBO J 2001,20(3):377–386. 10.1093\u002Femboj\u002F20.3.377\nSilveira JR, Raymond GJ, Hughson AG, Race RE, Sim VL, Hayes SF, Caughey B: The most infectious prion protein particles. Nature 2005,437(7056):257–261. 10.1038\u002Fnature03989\nMandybur TI: Cerebral amyloid angiopathy: the vascular pathology and complications. J Neuropathol Exp Neurol 1986,45(1):79–90. 10.1097\u002F00005072-198601000-00007\nVinters HV, Gilbert JJ: Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke 1983,14(6):924–928. 10.1161\u002F01.STR.14.6.924\nWeller RO: Pathology of cerebrospinal fluid and interstitial fluid of the CNS: significance for Alzheimer disease, prion disorders and multiple sclerosis. J Neuropathol Exp Neurol 1998,57(10):885–894. 10.1097\u002F00005072-199810000-00001\nWeller RO, Subash M, Preston SD, Mazanti I, Carare RO: Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol 2008,18(2):253–266.\nEurelings LS, Richard E, Carrano A, Eikelenboom P, van Gool WA, Rozemuller AJ: Dyshoric capillary cerebral amyloid angiopathy mimicking Creutzfeldt-Jakob disease. J Neurol Sci 2010,295(1–2):131–134.\nRichard E, Carrano A, Hoozemans JJ, van Horssen J, van Haastert ES, Eurelings LS, de Vries HE, Thal DR, Eikelenboom P, van Gool WA, Rozemuller AJ: Characteristics of dyshoric capillary cerebral amyloid angiopathy. J Neuropathol Exp Neurol 2010,69(11):1158–1167. 10.1097\u002FNEN.0b013e3181fab558\nAbbott NJ: Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 2004,45(4):545–552. 10.1016\u002Fj.neuint.2003.11.006\nCserr HF, Patlak CS: Secretion and Bulk Flow of Interstital Fluid. In Physiology and Pharmacology of the Blood–brain Barrier. Edited by: Bradbury MWB. Berlin: Springer; 1992:245–261.\nSchley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO: Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 2006,238(4):962–974. 10.1016\u002Fj.jtbi.2005.07.005",{"VOID":1635},"10.1186\u002F2051-5960-1-25","2024-05-27T12:14:22.534+00:00","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002F2051-5960-1-25",[1639,1654,1667,1684,1697],{"id":1640,"sortIndex":19,"researcher":18,"roles":1641,"affiliations":1642,"properties":1651,"displayName":1653,"givenName":18,"familyName":18},"04406e96-ff20-4842-b089-f90fdd72089b",[139],[1643],{"id":1644,"sortIndex":19,"affiliation":1645,"properties":18},"6c1e0fd4-87b0-4331-a483-7c74f7a06f16",{"id":1644,"createTime":18,"updateTime":18,"relativeEntities":1646,"slug":18,"properties":1647,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1650,"statistic":18},[],{"title":1648},{"VI":1649},"Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, USA",[],{"title":1652},{"VI":1653},"Alejandra Rangel",{"id":1655,"sortIndex":94,"researcher":18,"roles":1656,"affiliations":1657,"properties":1664,"displayName":1666,"givenName":18,"familyName":18},"9c1b01f0-25a6-479a-9773-d9bcd085f014",[139],[1658],{"id":1644,"sortIndex":19,"affiliation":1659,"properties":18},{"id":1644,"createTime":18,"updateTime":18,"relativeEntities":1660,"slug":18,"properties":1661,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1663,"statistic":18},[],{"title":1662},{"VI":1649},[],{"title":1665},{"VI":1666},"Brent Race",{"id":1668,"sortIndex":96,"researcher":18,"roles":1669,"affiliations":1670,"properties":1679,"displayName":1681,"givenName":18,"familyName":18},"1e7e0e21-8e40-4a22-bab3-205ff33ee43b",[139],[1671],{"id":1672,"sortIndex":19,"affiliation":1673,"properties":18},"f7d8de89-0394-4602-b7d3-b9ebabb6204d",{"id":1672,"createTime":18,"updateTime":18,"relativeEntities":1674,"slug":18,"properties":1675,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1678,"statistic":18},[],{"title":1676},{"EN":1677},"Department of Ophthalmology, Duke University Medical Center, Durham, USA",[],{"title":1680,"gsAuthor":1682},{"VI":1681},"Mikael Klingeborn",{"VOID":1683},"[\"GGTtQooAAAAJ\"]",{"id":1685,"sortIndex":101,"researcher":18,"roles":1686,"affiliations":1687,"properties":1694,"displayName":1696,"givenName":18,"familyName":18},"7bb9d0a0-ddf5-42a8-96db-492107346e31",[139],[1688],{"id":1644,"sortIndex":19,"affiliation":1689,"properties":18},{"id":1644,"createTime":18,"updateTime":18,"relativeEntities":1690,"slug":18,"properties":1691,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1693,"statistic":18},[],{"title":1692},{"VI":1649},[],{"title":1695},{"VI":1696},"James Striebel",{"id":1698,"sortIndex":100,"researcher":18,"roles":1699,"affiliations":1700,"properties":1716,"displayName":1718,"givenName":18,"familyName":18},"d224a7ac-d241-41ab-a245-024b3abf1d6e",[139],[1701,1707],{"id":1644,"sortIndex":19,"affiliation":1702,"properties":18},{"id":1644,"createTime":18,"updateTime":18,"relativeEntities":1703,"slug":18,"properties":1704,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1706,"statistic":18},[],{"title":1705},{"VI":1649},[],{"id":1708,"sortIndex":94,"affiliation":1709,"properties":1715},"62a79560-53e7-4029-adf6-b381fcb215f5",{"id":1708,"createTime":18,"updateTime":18,"relativeEntities":1710,"slug":18,"properties":1711,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1714,"statistic":18},[],{"title":1712},{"VI":1713},"Rocky Mountain Laboratories, Hamilton, USA",[],{},{"title":1717},{"VI":1718},"Bruce Chesebro",{"url":1637,"publisher":1720,"properties":1769},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":1721,"slug":10,"properties":1722,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":1725,"manageAffiliations":1738,"indexDatabases":1749,"url":91,"thumbnailPath":18,"statistic":1764,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":1723,"title":1724},{"VOID":13},{"EN":15},[1726,1730,1734],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":1727,"label":1728,"description":1729,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":1731,"label":1732,"description":1733,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":1735,"label":1736,"description":1737,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[1739,1744],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":1740,"slug":18,"properties":1741,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1743,"statistic":18},[],{"title":1742},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":1745,"slug":18,"properties":1746,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1748,"statistic":18},[],{"title":1747},{"EN":52},[],[1750,1757],{"id":56,"indexDatabase":1751,"url":69,"indexYears":18,"academicFieldIds":1756,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":1752,"label":1753,"description":1754,"key":65,"publicationTags":1755,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":1758,"url":84,"indexYears":85,"academicFieldIds":1763,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":1759,"label":1760,"description":1761,"key":81,"publicationTags":1762,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":1765,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":1766,"totalCitation":102,"totalCitationByYear":1767,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":1768,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":1770,"volume":1771},{"VOID":1374},{"VOID":767},"2013-06-19",2013,"2026-06-19T00:56:01.378+00:00",[67,90],{"id":1777,"createTime":1778,"updateTime":1779,"relativeEntities":1780,"slug":1781,"properties":1782,"entityType":128,"verifyStatus":129,"verifyTime":1794,"verifyNote":131,"languages":1795,"translateLanguages":18,"viewCount":19,"primaryUrl":1797,"fullTextUrl":18,"authors":1798,"publicationType":403,"publisherRelationship":2029,"citationCount":19,"citationInfo":2079,"publishDate":18,"publishYear":18,"citationAnalyzeStatus":1007,"lastCitationAnalyze":2081,"indexDatabases":2082,"openAccess":18,"references":2083,"isForceReanalyzing":462},"17777daa-f761-4729-811f-f69c1d54b829","2024-04-11T17:00:58.689+00:00","2026-05-19T18:05:50.185+00:00",[],"Proteomic-analysis-across-patient-iPSC-based-models-and-human-post-mortem-hippocampal-tissue-reveals-early-cellular-dysfunction-and-progression-of-Alzheimer-s-disease-pathogenesis",{"openalex":1783,"abstract":1785,"title":1787,"gsPaper":1789,"pm":1790,"doi":1792},{"VOID":1784},"W4386768297",{"EN":1786},"\u003Cjats:title>Abstract\u003C\u002Fjats:title>\u003Cjats:p>The hippocampus is a primary region affected in Alzheimer’s disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis by comparing patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus. Proteomic analysis of the graft enabled the identification of pathways and network dysfunction in AD patient brain cells, associated with increased levels of Aβ-42 and β-sheet structures. Interestingly, the host cells surrounding the AD graft also presented alterations in cellular biological pathways. Furthermore, proteomic analysis across human iPSC-based models and human post-mortem hippocampal tissue projected coherent longitudinal cellular changes indicative of early to end stage AD cellular pathogenesis. Our data showcase patient-based models to study the cell autonomous origin and progression of AD pathogenesis.\u003C\u002Fjats:p>\n                \u003Cjats:p>\u003Cjats:bold>Graphical Abstract\u003C\u002Fjats:bold>\u003C\u002Fjats:p>",{"EN":1788},"Proteomic analysis across patient iPSC-based models and human post-mortem hippocampal tissue reveals early cellular dysfunction and progression of Alzheimer’s disease pathogenesis",{"VOID":784},{"VOID":1791},"37715247",{"VOID":1793},"10.1186\u002Fs40478-023-01649-z","2024-06-23T02:39:14.629+00:00",[1796],"EN","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-023-01649-z",[1799,1818,1833,1850,1869,1886,1901,1920,1937,1954,1973,1990,2009],{"id":1800,"sortIndex":19,"researcher":18,"roles":1801,"affiliations":1802,"properties":1811,"displayName":1815,"givenName":18,"familyName":18},"b7c23975-39a9-43d8-99f6-208e315096bc",[],[1803],{"id":1804,"sortIndex":19,"affiliation":1805,"properties":18},"ad0fc696-2926-4b75-ba53-c5b4375da339",{"id":1804,"createTime":18,"updateTime":18,"relativeEntities":1806,"slug":18,"properties":1807,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1810,"statistic":18},[],{"title":1808},{"VI":1809},"Lund Stem Cell Center, Lund University, Lund, Sweden",[],{"orcid":1812,"title":1814,"openalex":1816},{"VOID":1813},"https:\u002F\u002Forcid.org\u002F0000-0002-1412-7403",{"EN":1815},"Yuriy Pomeshchik",{"VOID":1817},"A5006229908",{"id":1819,"sortIndex":94,"researcher":18,"roles":1820,"affiliations":1821,"properties":1828,"displayName":1830,"givenName":18,"familyName":18},"45d2b6cf-c3e7-40f3-991f-f90c5cdac9e7",[],[1822],{"id":1804,"sortIndex":19,"affiliation":1823,"properties":18},{"id":1804,"createTime":18,"updateTime":18,"relativeEntities":1824,"slug":18,"properties":1825,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1827,"statistic":18},[],{"title":1826},{"VI":1809},[],{"title":1829,"openalex":1831},{"EN":1830},"Erika Velásquez",{"VOID":1832},"A5081336394",{"id":1834,"sortIndex":96,"researcher":18,"roles":1835,"affiliations":1836,"properties":1845,"displayName":1847,"givenName":18,"familyName":18},"a0581d5c-0322-41b8-92be-f6d8f7b072c4",[],[1837],{"id":1838,"sortIndex":19,"affiliation":1839,"properties":18},"79edeafd-333a-4c85-901c-f2e5cfc56c01",{"id":1838,"createTime":18,"updateTime":18,"relativeEntities":1840,"slug":18,"properties":1841,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1844,"statistic":18},[],{"title":1842},{"EN":1843},"Clinical Protein Science & Imaging, Department of Biomedical Engineering, BMC D13, Lund University, Lund, Sweden",[],{"title":1846,"openalex":1848},{"EN":1847},"Jeovanis Gil",{"VOID":1849},"A5019411008",{"id":1851,"sortIndex":101,"researcher":18,"roles":1852,"affiliations":1853,"properties":1862,"displayName":1866,"givenName":18,"familyName":18},"a41b9e4b-4d6b-491f-97ca-1f4d966c6bf4",[],[1854],{"id":1855,"sortIndex":19,"affiliation":1856,"properties":18},"aadeefa1-f84f-4f68-b817-065feebad117",{"id":1855,"createTime":18,"updateTime":18,"relativeEntities":1857,"slug":18,"properties":1858,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1861,"statistic":18},[],{"title":1859},{"VI":1860},"Strategic Research Area MultiPark, Lund University, Lund, Sweden",[],{"orcid":1863,"title":1865,"openalex":1867},{"VOID":1864},"https:\u002F\u002Forcid.org\u002F0000-0003-1782-050X",{"EN":1866},"Oxana Klementieva",{"VOID":1868},"A5036281959",{"id":1870,"sortIndex":100,"researcher":18,"roles":1871,"affiliations":1872,"properties":1881,"displayName":1883,"givenName":18,"familyName":18},"7c2fc80f-f242-43e6-b73f-dfbcbb11591b",[],[1873],{"id":1874,"sortIndex":19,"affiliation":1875,"properties":18},"4585166d-abd1-4c4d-8f0b-961510379b25",{"id":1874,"createTime":18,"updateTime":18,"relativeEntities":1876,"slug":18,"properties":1877,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1880,"statistic":18},[],{"title":1878},{"EN":1879},"Lund University BioImaging Centre, Faculty of Medicine, Lund University, Lund, Sweden",[],{"title":1882,"openalex":1884},{"EN":1883},"Ritha Gidlöf",{"VOID":1885},"A5072027292",{"id":1887,"sortIndex":99,"researcher":18,"roles":1888,"affiliations":1889,"properties":1896,"displayName":1898,"givenName":18,"familyName":18},"ff9a9315-e977-4b2c-8d47-da1981913862",[],[1890],{"id":1874,"sortIndex":19,"affiliation":1891,"properties":18},{"id":1874,"createTime":18,"updateTime":18,"relativeEntities":1892,"slug":18,"properties":1893,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1895,"statistic":18},[],{"title":1894},{"EN":1879},[],{"title":1897,"openalex":1899},{"EN":1898},"Marie Sydoff",{"VOID":1900},"A5000007722",{"id":1902,"sortIndex":285,"researcher":18,"roles":1903,"affiliations":1904,"properties":1913,"displayName":1917,"givenName":18,"familyName":18},"ef74c561-d7fa-4411-9690-d964d2557bc7",[],[1905],{"id":1906,"sortIndex":19,"affiliation":1907,"properties":18},"2557d013-347f-4851-a985-2421f4d1a67c",{"id":1906,"createTime":18,"updateTime":18,"relativeEntities":1908,"slug":18,"properties":1909,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1912,"statistic":18},[],{"title":1910},{"EN":1911},"Laboratorio Di Neurogenetica, Dipartimento Di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino- NEUROFARBA, Università degli Studi di Firenze, 50134, Florence, Italy",[],{"orcid":1914,"title":1916,"openalex":1918},{"VOID":1915},"https:\u002F\u002Forcid.org\u002F0000-0002-4373-6611",{"EN":1917},"Silvia Bagnoli",{"VOID":1919},"A5073532878",{"id":1921,"sortIndex":308,"researcher":18,"roles":1922,"affiliations":1923,"properties":1930,"displayName":1934,"givenName":18,"familyName":18},"062e62e9-2b76-4c19-8f27-9eb2721f1e14",[],[1924],{"id":1906,"sortIndex":19,"affiliation":1925,"properties":18},{"id":1906,"createTime":18,"updateTime":18,"relativeEntities":1926,"slug":18,"properties":1927,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1929,"statistic":18},[],{"title":1928},{"EN":1911},[],{"orcid":1931,"title":1933,"openalex":1935},{"VOID":1932},"https:\u002F\u002Forcid.org\u002F0000-0001-9338-9040",{"EN":1934},"Benedetta Nacmias",{"VOID":1936},"A5060752663",{"id":1938,"sortIndex":333,"researcher":18,"roles":1939,"affiliations":1940,"properties":1947,"displayName":1951,"givenName":18,"familyName":18},"37936726-dd20-435e-91de-2f1b97ca35c9",[],[1941],{"id":1906,"sortIndex":19,"affiliation":1942,"properties":18},{"id":1906,"createTime":18,"updateTime":18,"relativeEntities":1943,"slug":18,"properties":1944,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1946,"statistic":18},[],{"title":1945},{"EN":1911},[],{"orcid":1948,"title":1950,"openalex":1952},{"VOID":1949},"https:\u002F\u002Forcid.org\u002F0000-0002-0380-6670",{"EN":1951},"Sandro Sorbi",{"VOID":1953},"A5011011071",{"id":1955,"sortIndex":354,"researcher":18,"roles":1956,"affiliations":1957,"properties":1966,"displayName":1970,"givenName":18,"familyName":18},"56c19f8a-c1f6-41b8-b479-5568eb965abc",[],[1958],{"id":1959,"sortIndex":19,"affiliation":1960,"properties":18},"885dc980-9292-4466-8ab8-f016c54c1faa",{"id":1959,"createTime":18,"updateTime":18,"relativeEntities":1961,"slug":18,"properties":1962,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1965,"statistic":18},[],{"title":1963},{"EN":1964},"Department of Experimental Medical Science, BMC C12, Faculty of Medicine, Lund University, Lund, Sweden",[],{"orcid":1967,"title":1969,"openalex":1971},{"VOID":1968},"https:\u002F\u002Forcid.org\u002F0000-0001-5327-8805",{"EN":1970},"Gunilla Westergren‐Thorsson",{"VOID":1972},"A5070146866",{"id":1974,"sortIndex":375,"researcher":18,"roles":1975,"affiliations":1976,"properties":1983,"displayName":1987,"givenName":18,"familyName":18},"3fea5529-1510-44f1-b171-52ab93fee3a0",[],[1977],{"id":1855,"sortIndex":19,"affiliation":1978,"properties":18},{"id":1855,"createTime":18,"updateTime":18,"relativeEntities":1979,"slug":18,"properties":1980,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":1982,"statistic":18},[],{"title":1981},{"VI":1860},[],{"orcid":1984,"title":1986,"openalex":1988},{"VOID":1985},"https:\u002F\u002Forcid.org\u002F0000-0002-5500-6325",{"EN":1987},"Gunnar K. Gouras",{"VOID":1989},"A5065797283",{"id":1991,"sortIndex":1303,"researcher":18,"roles":1992,"affiliations":1993,"properties":2002,"displayName":2006,"givenName":18,"familyName":18},"da463302-bcf2-4c70-80b2-c4a4690436d0",[],[1994],{"id":1995,"sortIndex":19,"affiliation":1996,"properties":18},"8237e1ce-5539-402d-b4d3-23f87b70fb48",{"id":1995,"createTime":18,"updateTime":18,"relativeEntities":1997,"slug":18,"properties":1998,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2001,"statistic":18},[],{"title":1999},{"EN":2000},"Swedish National Infrastructure for Biological Mass Spectrometry (BioMS), Lund University, Lund, Sweden",[],{"orcid":2003,"title":2005,"openalex":2007},{"VOID":2004},"https:\u002F\u002Forcid.org\u002F0000-0003-4373-5616",{"EN":2006},"Melinda Rezeli",{"VOID":2008},"A5088372878",{"id":2010,"sortIndex":2011,"researcher":18,"roles":2012,"affiliations":2013,"properties":2022,"displayName":2026,"givenName":18,"familyName":18},"e5935b33-4ddb-4f5f-aa09-2f06137b526c",12,[],[2014],{"id":2015,"sortIndex":19,"affiliation":2016,"properties":18},"b5a581a8-b676-4a4c-a4f9-8e5f911b64f9",{"id":2015,"createTime":18,"updateTime":18,"relativeEntities":2017,"slug":18,"properties":2018,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2021,"statistic":18},[],{"title":2019},{"VI":2020},"Lund Stem Cell Center, Lund University, 22184 Lund, Sweden",[],{"orcid":2023,"title":2025,"openalex":2027},{"VOID":2024},"https:\u002F\u002Forcid.org\u002F0000-0002-5532-4964",{"EN":2026},"Laurent Roybon",{"VOID":2028},"A5060670053",{"url":18,"publisher":2030,"properties":18},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2031,"slug":10,"properties":2032,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2035,"manageAffiliations":2048,"indexDatabases":2059,"url":91,"thumbnailPath":18,"statistic":2074,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":2033,"title":2034},{"VOID":13},{"EN":15},[2036,2040,2044],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2037,"label":2038,"description":2039,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":2041,"label":2042,"description":2043,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":2045,"label":2046,"description":2047,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[2049,2054],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":2050,"slug":18,"properties":2051,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2053,"statistic":18},[],{"title":2052},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":2055,"slug":18,"properties":2056,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2058,"statistic":18},[],{"title":2057},{"EN":52},[],[2060,2067],{"id":56,"indexDatabase":2061,"url":69,"indexYears":18,"academicFieldIds":2066,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":2062,"label":2063,"description":2064,"key":65,"publicationTags":2065,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":2068,"url":84,"indexYears":85,"academicFieldIds":2073,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":2069,"label":2070,"description":2071,"key":81,"publicationTags":2072,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":2075,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":2076,"totalCitation":102,"totalCitationByYear":2077,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":2078,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"total":19,"publishYear":18,"statisticByYear":2080},{},"2026-05-19T18:05:50.184+00:00",[],[2084,2088,2092,2096,2100,2104,2108,2112,2116,2120,2124,2128,2132,2136,2140,2144,2148,2152,2156,2160,2164,2168,2172,2176,2180,2184,2188,2192,2196,2200,2204,2208,2212,2216,2220,2224,2228,2232,2236,2240,2244,2248,2252,2255,2259,2263,2267,2271,2275,2279,2283,2287,2291,2295,2299,2303,2307,2311,2315,2319,2323,2327,2331,2335,2339,2343,2347,2351,2355,2359,2363,2367,2371,2375,2379,2383,2387,2391,2395,2399,2403,2406,2410,2414],{"id":18,"text":2085,"url":18,"identifiers":2086},"Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368(9533):387–403",{"doi":2087},"10.1016\u002FS0140-6736(06)69113-7",{"id":18,"text":2089,"url":18,"identifiers":2090},"Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26(40):10129–10140",{"doi":2091},"10.1523\u002FJNEUROSCI.1202-06.2006",{"id":18,"text":2093,"url":18,"identifiers":2094},"Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221",{"doi":2095},"10.1126\u002Fscience.1158799",{"id":18,"text":2097,"url":18,"identifiers":2098},"Sasaguri H, Hashimoto S, Watamura N, Sato K, Takamura R, Nagata K, Tsubuki S, Ohshima T, Yoshiki A, Sato K, Kumita W, Sasaki E, Kitazume S, Nilsson P, Winblad B, Saito T, Iwata N, Saido TC (2022) Recent advances in the modeling of Alzheimer’s disease. Front Neurosci 16:807473",{"doi":2099},"10.3389\u002Ffnins.2022.807473",{"id":18,"text":2101,"url":18,"identifiers":2102},"Konttinen H, Cabral-da-Silva MEC, Ohtonen S, Wojciechowski S, Shakirzyanova A, Caligola S, Giugno R, Ishchenko Y, Hernandez D, Fazaludeen MF, Eamen S, Budia MG, Fagerlund I, Scoyni F, Korhonen P, Huber N, Haapasalo A, Hewitt AW, Vickers J, Smith GC, Oksanen M, Graff C, Kanninen KM, Lehtonen S, Propson N, Schwartz MP, Pebay A, Koistinaho J, Ooi L, Malm T (2019) PSEN1DeltaE9, APPswe, and APOE4 confer disparate phenotypes in human iPSC-derived microglia. Stem Cell Reports 13(4):669–683",{"doi":2103},"10.1016\u002Fj.stemcr.2019.08.004",{"id":18,"text":2105,"url":18,"identifiers":2106},"Kondo T, Asai M, Tsukita K, Kutoku Y, Ohsawa Y, Sunada Y, Imamura K, Egawa N, Yahata N, Okita K, Takahashi K, Asaka I, Aoi T, Watanabe A, Watanabe K, Kadoya C, Nakano R, Watanabe D, Maruyama K, Hori O, Hibino S, Choshi T, Nakahata T, Hioki H, Kaneko T, Naitoh M, Yoshikawa K, Yamawaki S, Suzuki S, Hata R, Ueno S, Seki T, Kobayashi K, Toda T, Murakami K, Irie K, Klein WL, Mori H, Asada T, Takahashi R, Iwata N, Yamanaka S, Inoue H (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12(4):487–496",{"doi":2107},"10.1016\u002Fj.stem.2013.01.009",{"id":18,"text":2109,"url":18,"identifiers":2110},"Pomeshchik Y, Klementieva O, Gil J, Martinsson I, Hansen MG, de Vries T, Sancho-Balsells A, Russ K, Savchenko E, Collin A, Vaz AR, Bagnoli S, Nacmias B, Rampon C, Sorbi S, Brites D, Marko-Varga G, Kokaia Z, Rezeli M, Gouras GK, Roybon L (2020) Human iPSC-derived hippocampal spheroids: an innovative tool for stratifying alzheimer disease patient-specific cellular phenotypes and developing therapies. Stem Cell Reports 15(1):256–273",{"doi":2111},"10.1016\u002Fj.stemcr.2020.06.001",{"id":18,"text":2113,"url":18,"identifiers":2114},"Penney J, Ralvenius WT, Tsai LH (2020) Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol Psychiatry 25(1):148–167",{"doi":2115},"10.1038\u002Fs41380-019-0468-3",{"id":18,"text":2117,"url":18,"identifiers":2118},"Verheijen MCT, Krauskopf J, Caiment F, Nazaruk M, Wen QF, van Herwijnen MHM, Hauser DA, Gajjar M, Verfaillie C, Vermeiren Y, De Deyn PP, Wittens MMJ, Sieben A, Engelborghs S, Dejonckheere W, Princen K, Griffioen G, Roggen EL, Briede JJ (2022) iPSC-derived cortical neurons to study sporadic Alzheimer disease: a transcriptome comparison with post-mortem brain samples. Toxicol Lett 356:89–99",{"doi":2119},"10.1016\u002Fj.toxlet.2021.12.009",{"id":18,"text":2121,"url":18,"identifiers":2122},"Zhao J, Fu Y, Yamazaki Y, Ren Y, Davis MD, Liu CC, Lu W, Wang X, Chen K, Cherukuri Y, Jia L, Martens YA, Job L, Shue F, Nguyen TT, Younkin SG, Graff-Radford NR, Wszolek ZK, Brafman DA, Asmann YW, Ertekin-Taner N, Kanekiyo T, Bu G (2020) APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer’s disease patient iPSC-derived cerebral organoids. Nat Commun 11(1):5540",{"doi":2123},"10.1038\u002Fs41467-020-19264-0",{"id":18,"text":2125,"url":18,"identifiers":2126},"Kwart D, Gregg A, Scheckel C, Murphy EA, Paquet D, Duffield M, Tessier-Lavigne M (2019) A large panel of isogenic APP and PSEN1 mutant human iPSC neurons reveals shared endosomal abnormalities mediated by APP β-CTFs, not Aβ. Neuron 104(2):256–270",{"doi":2127},"10.1016\u002Fj.neuron.2019.07.010",{"id":18,"text":2129,"url":18,"identifiers":2130},"Muratore CR, Rice HC, Srikanth P, Callahan DG, Shin T, Benjamin LN, Walsh DM, Selkoe DJ, Young-Pearse TL (2014) The familial Alzheimer’s disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Hum Mol Genet 23(13):3523–3536",{"doi":2131},"10.1093\u002Fhmg\u002Fddu064",{"id":18,"text":2133,"url":18,"identifiers":2134},"Sproul AA, Jacob S, Pre D, Kim SH, Nestor MW, Navarro-Sobrino M, Santa-Maria I, Zimmer M, Aubry S, Steele JW, Kahler DJ, Dranovsky A, Arancio O, Crary JF, Gandy S, Noggle SA (2014) Characterization and molecular profiling of PSEN1 familial Alzheimer’s disease iPSC-derived neural progenitors. PLoS ONE 9(1):e84547",{"doi":2135},"10.1371\u002Fjournal.pone.0084547",{"id":18,"text":2137,"url":18,"identifiers":2138},"Windrem MS, Osipovitch M, Liu Z, Bates J, Chandler-Militello D, Zou L, Goldman SA (2017) Human iPSC glial mouse chimeras reveal glial contributions to schizophrenia. Cell Stem Cell 21(2):195–208",{"doi":2139},"10.1016\u002Fj.stem.2017.06.012",{"id":18,"text":2141,"url":18,"identifiers":2142},"Osipovitch M, Martinez AA, Mariani JN, Cornwell A, Dhaliwal S, Zou L, Goldman SA (2019) Human ESC-derived chimeric mouse models of Huntington’s disease reveal cell-intrinsic defects in glial progenitor cell differentiation. Cell Stem Cell 24(1):107–122",{"doi":2143},"10.1016\u002Fj.stem.2018.11.010",{"id":18,"text":2145,"url":18,"identifiers":2146},"Najm R, Zalocusky KA, Zilberter M, Yoon SY, Hao Y, Koutsodendris N, Nelson M, Rao A, Taubes A, Jones EA, Huang Y (2020) In vivo chimeric Alzheimer’s disease modeling of apolipoprotein E4 toxicity in human neurons. Cell Rep 32(4):107962",{"doi":2147},"10.1016\u002Fj.celrep.2020.107962",{"id":18,"text":2149,"url":18,"identifiers":2150},"Espuny-Camacho I, Arranz AM, Fiers M, Snellinx A, Ando K, Munck S, De Strooper B (2017) Hallmarks of Alzheimer’s disease in stem-cell-derived human neurons transplanted into mouse brain. Neuron 93(5):1066–1081",{"doi":2151},"10.1016\u002Fj.neuron.2017.02.001",{"id":18,"text":2153,"url":18,"identifiers":2154},"Preman P, Tcw J, Calafate S, Snellinx A, Alfonso-Triguero M, Corthout N, Munck S, Thal DR, Goate AM, De Strooper B, Arranz AM (2021) Human iPSC-derived astrocytes transplanted into the mouse brain undergo morphological changes in response to amyloid-beta plaques. Mol Neurodegener 16(1):68",{"doi":2155},"10.1186\u002Fs13024-021-00487-8",{"id":18,"text":2157,"url":18,"identifiers":2158},"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239–259",{"doi":2159},"10.1007\u002FBF00308809",{"id":18,"text":2161,"url":18,"identifiers":2162},"Matsuda H, Ito K, Ishii K, Shimosegawa E, Okazawa H, Mishina M, Mizumura S, Ishii K, Okita K, Shigemoto Y, Kato T, Takenaka A, Kaida H, Hanaoka K, Matsunaga K, Hatazawa J, Ikawa M, Tsujikawa T, Morooka M, Ishibashi K, Kameyama M, Yamao T, Miwa K, Ogawa M, Sato N (2020) Quantitative evaluation of (18)F-flutemetamol PET in patients with cognitive impairment and suspected Alzheimer’s disease: a multicenter study. Front Neurol 11:578753",{"doi":2163},"10.3389\u002Ffneur.2020.578753",{"id":18,"text":2165,"url":18,"identifiers":2166},"Bouter C, Bouter Y (2019) (18)F-FDG-PET in mouse models of Alzheimer’s disease. Front Med (Lausanne) 6:71",{"doi":2167},"10.3389\u002Ffmed.2019.00071",{"id":18,"text":2169,"url":18,"identifiers":2170},"Klementieva O, Willen K, Martinsson I, Israelsson B, Engdahl A, Cladera J, Uvdal P, Gouras GK (2017) Pre-plaque conformational changes in Alzheimer’s disease-linked Abeta and APP. Nat Commun 8:14726",{"doi":2171},"10.1038\u002Fncomms14726",{"id":18,"text":2173,"url":18,"identifiers":2174},"Wu M, Zhang M, Yin X, Chen K, Hu Z, Zhou Q, Cao X, Chen Z, Liu D (2021) The role of pathological tau in synaptic dysfunction in Alzheimer’s diseases. Transl Neurodegener 10(1):45",{"doi":2175},"10.1186\u002Fs40035-021-00270-1",{"id":18,"text":2177,"url":18,"identifiers":2178},"Kayed R, Head E, Sarsoza F, Saing T, Cotman CW, Necula M, Margol L, Wu J, Breydo L, Thompson JL, Rasool S, Gurlo T, Butler P, Glabe CG (2007) Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol Neurodegener 2:18",{"doi":2179},"10.1186\u002F1750-1326-2-18",{"id":18,"text":2181,"url":18,"identifiers":2182},"Delacourte A (1990) General and dramatic glial reaction in Alzheimer brains. Neurology 40(1):33–37",{"doi":2183},"10.1212\u002FWNL.40.1.33",{"id":18,"text":2185,"url":18,"identifiers":2186},"Reichenbach N, Delekate A, Plescher M, Schmitt F, Krauss S, Blank N, Petzold GC (2019) Inhibition of Stat3-mediated astrogliosis ameliorates pathology in an Alzheimer’s disease model. EMBO Mol Med 11(2):e9665",{"doi":2187},"10.15252\u002Femmm.201809665",{"id":18,"text":2189,"url":18,"identifiers":2190},"Toral-Rios D, Patiño-López G, Gómez-Lira G, Gutiérrez R, Becerril-Pérez F, Rosales-Córdova A, Campos-Peña V (2020) Activation of STAT3 regulates reactive astrogliosis and neuronal death induced by AβO neurotoxicity. Int J Mol Sci 21(20):7458",{"doi":2191},"10.3390\u002Fijms21207458",{"id":18,"text":2193,"url":18,"identifiers":2194},"Bastin G, Heximer SP (2013) Rab family proteins regulate the endosomal trafficking and function of RGS4. J Biol Chem 288(30):21836–21849",{"doi":2195},"10.1074\u002Fjbc.M113.466888",{"id":18,"text":2197,"url":18,"identifiers":2198},"Tam SY, Lilla JN, Chen CC, Kalesnikoff J, Tsai M (2015) RabGEF1\u002FRabex-5 regulates TrkA-mediated neurite outgrowth and nmda-induced signaling activation in NGF-differentiated PC12 cells. PLoS ONE 10(11):e0142935",{"doi":2199},"10.1371\u002Fjournal.pone.0142935",{"id":18,"text":2201,"url":18,"identifiers":2202},"Nagano M, Toshima JY, Siekhaus DE, Toshima J (2019) Rab5-mediated endosome formation is regulated at the trans-Golgi network. Commun Biol 2:419",{"doi":2203},"10.1038\u002Fs42003-019-0670-5",{"id":18,"text":2205,"url":18,"identifiers":2206},"Neff RA, Wang M, Vatansever S, Guo L, Ming C, Wang Q, Zhang B (2021) Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets. Sci Adv 7(2):eabb5398",{"doi":2207},"10.1126\u002Fsciadv.abb5398",{"id":18,"text":2209,"url":18,"identifiers":2210},"Okano H, Morimoto S (2022) iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders. Cell Stem Cell 29(2):189–208",{"doi":2211},"10.1016\u002Fj.stem.2022.01.007",{"id":18,"text":2213,"url":18,"identifiers":2214},"Tcw J, Qian L, Pipalia NH, Chao MJ, Liang SA, Shi Y, Jain BR, Bertelsen SE, Kapoor M, Marcora E, Sikora E, Andrews EJ, Martini AC, Karch CM, Head E, Holtzman DM, Zhang B, Wang M, Maxfield FR, Poon WW, Goate AM (2022) Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell 185(13):2213–2233",{"doi":2215},"10.1016\u002Fj.cell.2022.05.017",{"id":18,"text":2217,"url":18,"identifiers":2218},"Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen Š, Olivé MG, Koistinaho J (2017) PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer’s disease. Stem Cell Reports 9(6):1885–1897",{"doi":2219},"10.1016\u002Fj.stemcr.2017.10.016",{"id":18,"text":2221,"url":18,"identifiers":2222},"Shimada H, Sato Y, Sasaki T, Shimozawa A, Imaizumi K, Shindo T, Miyao S, Kiyama K, Kondo T, Shibata S, Ishii S, Kuromitsu J, Aoyagi H, Ito D, Okano H (2022) A next-generation iPSC-derived forebrain organoid model of tauopathy with tau fibrils by AAV-mediated gene transfer. Cell Rep Methods 2(9):100289",{"doi":2223},"10.1016\u002Fj.crmeth.2022.100289",{"id":18,"text":2225,"url":18,"identifiers":2226},"Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand KJ, De Luca GC, Crary JF, Casaccia P, Buxbaum JD, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B (2016) Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease. Genome Med 8(1):104",{"doi":2227},"10.1186\u002Fs13073-016-0355-3",{"id":18,"text":2229,"url":18,"identifiers":2230},"Wang M, Beckmann ND, Roussos P, Wang E, Zhou X, Wang Q, Ming C, Neff R, Ma W, Fullard JF, Hauberg ME, Bendl J, Peters MA, Logsdon B, Wang P, Mahajan M, Mangravite LM, Dammer EB, Duong DM, Lah JJ, Seyfried NT, Levey AI, Buxbaum JD, Ehrlich M, Gandy S, Katsel P, Haroutunian V, Schadt E, Zhang B (2018) The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer’s disease. Sci Data 5:180185",{"doi":2231},"10.1038\u002Fsdata.2018.185",{"id":18,"text":2233,"url":18,"identifiers":2234},"Nedergaard M, Goldman SA (2020) Glymphatic failure as a final common pathway to dementia. Science 370(6512):50–56",{"doi":2235},"10.1126\u002Fscience.abb8739",{"id":18,"text":2237,"url":18,"identifiers":2238},"Van Dorpe J, Smeijers L, Dewachter I, Nuyens D, Spittaels K, Van Den Haute C, Mercken M, Moechars D, Laenen I, Kuiperi C, Bruynseels K, Tesseur I, Loos R, Vanderstichele H, Checler F, Sciot R, Van Leuven F (2000) Prominent cerebral amyloid angiopathy in transgenic mice overexpressing the london mutant of human APP in neurons. Am J Pathol 157(4):1283–1298",{"doi":2239},"10.1016\u002FS0002-9440(10)64644-5",{"id":18,"text":2241,"url":18,"identifiers":2242},"Albert K, Niskanen J, Kälvälä S, Lehtonen Š (2021) Utilising induced pluripotent stem cells in neurodegenerative disease research: focus on glia. Int J Mol Sci 22(9):4334",{"doi":2243},"10.3390\u002Fijms22094334",{"id":18,"text":2245,"url":18,"identifiers":2246},"Jones VC, Atkinson-Dell R, Verkhratsky A, Mohamet L (2017) Aberrant iPSC-derived human astrocytes in Alzheimer’s disease. Cell Death Dis 8(3):e2696",{"doi":2247},"10.1038\u002Fcddis.2017.89",{"id":18,"text":2249,"url":18,"identifiers":2250},"Habib N, McCabe C, Medina S, Varshavsky M, Kitsberg D, Dvir-Szternfeld R, Green G, Dionne D, Nguyen L, Marshall JL, Chen F, Zhang F, Kaplan T, Regev A, Schwartz M (2020) Disease-associated astrocytes in Alzheimer’s disease and aging. Nat Neurosci 23(6):701–706",{"doi":2251},"10.1038\u002Fs41593-020-0624-8",{"id":18,"text":2253,"url":18,"identifiers":2254},"Salcedo C, Andersen JV, Vinten KT, Pinborg LH, Waagepetersen HS, Freude KK, Aldana BI (2021) Functional metabolic mapping reveals highly active branched-chain amino acid metabolism in human astrocytes. Which Is Impaired in iPSC-Derived Astrocytes in Alzheimer’s Disease, Front Aging Neurosci 13:736580",{},{"id":18,"text":2256,"url":18,"identifiers":2257},"Mathys H, Davila-Velderrain J, Peng Z, Gao F, Mohammadi S, Young JZ, Menon M, He L, Abdurrob F, Jiang X, Martorell AJ, Ransohoff RM, Hafler BP, Bennett DA, Kellis M, Tsai LH (2019) Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570(7761):332–337",{"doi":2258},"10.1038\u002Fs41586-019-1195-2",{"id":18,"text":2260,"url":18,"identifiers":2261},"Grubman A, Chew G, Ouyang JF, Sun G, Choo XY, McLean C, Simmons RK, Buckberry S, Vargas-Landin DB, Poppe D, Pflueger J, Lister R, Rackham OJL, Petretto E, Polo JM (2019) A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat Neurosci 22(12):2087–2097",{"doi":2262},"10.1038\u002Fs41593-019-0539-4",{"id":18,"text":2264,"url":18,"identifiers":2265},"Smith AM, Davey K, Tsartsalis S, Khozoie C, Fancy N, Tang SS, Liaptsi E, Weinert M, McGarry A, Muirhead RCJ, Gentleman S, Owen DR, Matthews PM (2022) Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology. Acta Neuropathol 143(1):75–91",{"doi":2266},"10.1007\u002Fs00401-021-02372-6",{"id":18,"text":2268,"url":18,"identifiers":2269},"Russ K, Teku G, Bousset L, Redeker V, Piel S, Savchenko E, Pomeshchik Y, Savistchenko J, Stummann TC, Azevedo C, Collin A, Goldwurm S, Fog K, Elmer E, Vihinen M, Melki R, Roybon L (2021) TNF-alpha and alpha-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration. Cell Rep 34(12):108895",{"doi":2270},"10.1016\u002Fj.celrep.2021.108895",{"id":18,"text":2272,"url":18,"identifiers":2273},"Wang W, Zhao F, Ma X, Perry G, Zhu X (2020) Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances. Mol Neurodegener 15(1):30",{"doi":2274},"10.1186\u002Fs13024-020-00376-6",{"id":18,"text":2276,"url":18,"identifiers":2277},"Cenini G, Voos W (2019) Mitochondria as potential targets in alzheimer disease therapy: an update. Front Pharmacol 10:902",{"doi":2278},"10.3389\u002Ffphar.2019.00902",{"id":18,"text":2280,"url":18,"identifiers":2281},"Kobro-Flatmoen A, Lagartos-Donate MJ, Aman Y, Edison P, Witter MP, Fang EF (2021) Re-emphasizing early Alzheimer’s disease pathology starting in select entorhinal neurons, with a special focus on mitophagy. Ageing Res Rev 67:101307",{"doi":2282},"10.1016\u002Fj.arr.2021.101307",{"id":18,"text":2284,"url":18,"identifiers":2285},"Hooper C, Killick R, Lovestone S (2008) The GSK3 hypothesis of Alzheimer’s disease. J Neurochem 104(6):1433–1439",{"doi":2286},"10.1111\u002Fj.1471-4159.2007.05194.x",{"id":18,"text":2288,"url":18,"identifiers":2289},"Ma T (2014) GSK3 in Alzheimer’s disease: mind the isoforms. J Alzheimers Dis 39(4):707–710",{"doi":2290},"10.3233\u002FJAD-131661",{"id":18,"text":2292,"url":18,"identifiers":2293},"Lauretti E, Dincer O, Pratico D (2020) Glycogen synthase kinase-3 signaling in Alzheimer’s disease. Biochim Biophys Acta Mol Cell Res 1867(5):118664",{"doi":2294},"10.1016\u002Fj.bbamcr.2020.118664",{"id":18,"text":2296,"url":18,"identifiers":2297},"Chudobova J, Zempel H (2023) Microtubule affinity regulating kinase (MARK\u002FPar1) isoforms differentially regulate Alzheimer-like TAU missorting and Abeta-mediated synapse pathology. Neural Regen Res 18(2):335–336",{"doi":2298},"10.4103\u002F1673-5374.346477",{"id":18,"text":2300,"url":18,"identifiers":2301},"Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM (2017) Synaptic impairment in Alzheimer’s disease: a dysregulated symphony. Trends Neurosci 40(6):347–357",{"doi":2302},"10.1016\u002Fj.tins.2017.04.002",{"id":18,"text":2304,"url":18,"identifiers":2305},"Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27(10):1372–1384",{"doi":2306},"10.1016\u002Fj.neurobiolaging.2005.09.012",{"id":18,"text":2308,"url":18,"identifiers":2309},"Aoyagi A, Condello C, Stöhr J, Yue W, Rivera BM, Lee JC, Prusiner SB (2019) Aβ and tau prion-like activities decline with longevity in the Alzheimer’s disease human brain. Sci Trans Med 11(490):eaat8462",{"doi":2310},"10.1126\u002Fscitranslmed.aat8462",{"id":18,"text":2312,"url":18,"identifiers":2313},"Gomez-Gutierrez R, Morales R (2020) The prion-like phenomenon in Alzheimer’s disease: evidence of pathology transmission in humans. PLoS Pathog 16(10):e1009004",{"doi":2314},"10.1371\u002Fjournal.ppat.1009004",{"id":18,"text":2316,"url":18,"identifiers":2317},"Hu NW, Corbett GT, Moore S, Klyubin I, O’Malley TT, Walsh DM, Livesey FJ, Rowan MJ (2018) Extracellular forms of abeta and tau from iPSC models of Alzheimer’s disease disrupt synaptic plasticity. Cell Rep 23(7):1932–1938",{"doi":2318},"10.1016\u002Fj.celrep.2018.04.040",{"id":18,"text":2320,"url":18,"identifiers":2321},"Ayers JI, Giasson BI, Borchelt DR (2018) Prion-like spreading in tauopathies. Biol Psychiatry 83(4):337–346",{"doi":2322},"10.1016\u002Fj.biopsych.2017.04.003",{"id":18,"text":2324,"url":18,"identifiers":2325},"Condello C, Stoehr J (2018) Abeta propagation and strains: Implications for the phenotypic diversity in Alzheimer’s disease. Neurobiol Dis 109(Pt B):191–200",{"doi":2326},"10.1016\u002Fj.nbd.2017.03.014",{"id":18,"text":2328,"url":18,"identifiers":2329},"Roos TT, Garcia MG, Martinsson I, Mabrouk R, Israelsson B, Deierborg T, Kobro-Flatmoen A, Tanila H, Gouras GK (2021) Neuronal spreading and plaque induction of intracellular Abeta and its disruption of Abeta homeostasis. Acta Neuropathol 142(4):669–687",{"doi":2330},"10.1007\u002Fs00401-021-02345-9",{"id":18,"text":2332,"url":18,"identifiers":2333},"Sleegers K, Brouwers N, Gijselinck I, Theuns J, Goossens D, Wauters J, Del-Favero J, Cruts M, van Duijn CM, Van Broeckhoven C (2006) APP duplication is sufficient to cause early onset Alzheimer’s dementia with cerebral amyloid angiopathy. Brain 129(Pt 11):2977–2983",{"doi":2334},"10.1093\u002Fbrain\u002Fawl203",{"id":18,"text":2336,"url":18,"identifiers":2337},"Fortea J, Zaman SH, Hartley S, Rafii MS, Head E, Carmona-Iragui M (2021) Alzheimer’s disease associated with Down syndrome: a genetic form of dementia. Lancet Neurol 20(11):930–942",{"doi":2338},"10.1016\u002FS1474-4422(21)00245-3",{"id":18,"text":2340,"url":18,"identifiers":2341},"Rovelet-Lecrux A, Hannequin D, Raux G, Le Meur N, Laquerriere A, Vital A, Dumanchin C, Feuillette S, Brice A, Vercelletto M, Dubas F, Frebourg T, Campion D (2006) APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. Nat Genet 38(1):24–26",{"doi":2342},"10.1038\u002Fng1718",{"id":18,"text":2344,"url":18,"identifiers":2345},"Davis-Salinas J, Van Nostrand WE (1995) Amyloid beta-protein aggregation nullifies its pathologic properties in cultured cerebrovascular smooth muscle cells. J Biol Chem 270(36):20887–20890",{"doi":2346},"10.1074\u002Fjbc.270.36.20887",{"id":18,"text":2348,"url":18,"identifiers":2349},"Saura CA, Deprada A, Capilla-Lopez MD, Parra-Damas A (2023) Revealing cell vulnerability in Alzheimer’s disease by single-cell transcriptomics. Semin Cell Dev Biol 139:73–83",{"doi":2350},"10.1016\u002Fj.semcdb.2022.05.007",{"id":18,"text":2352,"url":18,"identifiers":2353},"Blanchard JW, Akay LA, Davila-Velderrain J, von Maydell D, Mathys H, Davidson SM, Effenberger A, Chen CY, Maner-Smith K, Hajjar I, Ortlund EA, Bula M, Agbas E, Ng A, Jiang X, Kahn M, Blanco-Duque C, Lavoie N, Liu L, Reyes R, Lin YT, Ko T, R’Bibo L, Ralvenius WT, Bennett DA, Cam HP, Kellis M, Tsai LH (2022) APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature 611(7937):769–779",{"doi":2354},"10.1038\u002Fs41586-022-05439-w",{"id":18,"text":2356,"url":18,"identifiers":2357},"Nasrabady SE, Rizvi B, Goldman JE, Brickman AM (2018) White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta Neuropathol Commun 6(1):22",{"doi":2358},"10.1186\u002Fs40478-018-0515-3",{"id":18,"text":2360,"url":18,"identifiers":2361},"Azevedo C, Teku G, Pomeshchik Y, Reyes JF, Chumarina M, Russ K, Savchenko E, Hammarberg A, Lamas NJ, Collin A, Gouras GK, Klementieva O, Hallbeck M, Taipa R, Vihinen M, Roybon L (2022) Parkinson’s disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein-induced changes in maturation and immune reactive properties. Proc Natl Acad Sci U S A 119(12):e2111405119",{"doi":2362},"10.1073\u002Fpnas.2111405119",{"id":18,"text":2364,"url":18,"identifiers":2365},"Venegas C, Kumar S, Franklin BS, Dierkes T, Brinkschulte R, Tejera D, Vieira-Saecker A, Schwartz S, Santarelli F, Kummer MP, Griep A, Gelpi E, Beilharz M, Riedel D, Golenbock DT, Geyer M, Walter J, Latz E, Heneka MT (2017) Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer’s disease. Nature 552(7685):355–361",{"doi":2366},"10.1038\u002Fnature25158",{"id":18,"text":2368,"url":18,"identifiers":2369},"Gratuze M, Leyns CEG, Holtzman DM (2018) New insights into the role of TREM2 in Alzheimer’s disease. Mol Neurodegener 13(1):66",{"doi":2370},"10.1186\u002Fs13024-018-0298-9",{"id":18,"text":2372,"url":18,"identifiers":2373},"Fagerlund I, Dougalis A, Shakirzyanova A, Gómez-Budia M, Pelkonen A, Konttinen H, Malm T (2021) Microglia-like cells promote neuronal functions in cerebral organoids. Cells 11(1):124",{"doi":2374},"10.3390\u002Fcells11010124",{"id":18,"text":2376,"url":18,"identifiers":2377},"Mansour AA, Goncalves JT, Bloyd CW, Li H, Fernandes S, Quang D, Johnston S, Parylak SL, Jin X, Gage FH (2018) An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol 36(5):432–441",{"doi":2378},"10.1038\u002Fnbt.4127",{"id":18,"text":2380,"url":18,"identifiers":2381},"Revah O, Gore F, Kelley KW, Andersen J, Sakai N, Chen X, Li MY, Birey F, Yang X, Saw NL, Baker SW, Amin ND, Kulkarni S, Mudipalli R, Cui B, Nishino S, Grant GA, Knowles JK, Shamloo M, Huguenard JR, Deisseroth K, Pasca SP (2022) Maturation and circuit integration of transplanted human cortical organoids. Nature 610(7931):319–326",{"doi":2382},"10.1038\u002Fs41586-022-05277-w",{"id":18,"text":2384,"url":18,"identifiers":2385},"Chumarina M, Russ K, Azevedo C, Heuer A, Pihl M, Collin A, Roybon L (2019) Cellular alterations identified in pluripotent stem cell-derived midbrain spheroids generated from a female patient with progressive external ophthalmoplegia and parkinsonism who carries a novel variation (p. Q811R) in the POLG1 gene. Acta Neuropathol Commun 7:1–19",{"doi":2386},"10.1186\u002Fs40478-019-0863-7",{"id":18,"text":2388,"url":18,"identifiers":2389},"Lagomarsino VN, Pearse RV 2nd, Liu L, Hsieh YC, Fernandez MA, Vinton EA, Paull D, Felsky D, Tasaki S, Gaiteri C, Vardarajan B, Lee H, Muratore CR, Benoit CR, Chou V, Fancher SB, He A, Merchant JP, Duong DM, Martinez H, Zhou M, Bah F, Vicent MA, Stricker JMS, Xu J, Dammer EB, Levey AI, Chibnik LB, Menon V, Seyfried NT, De Jager PL, Noggle S, Selkoe DJ, Bennett DA, Young-Pearse TL (2021) Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors. Neuron 109(21):3402–3420",{"doi":2390},"10.1016\u002Fj.neuron.2021.08.003",{"id":18,"text":2392,"url":18,"identifiers":2393},"Brundin P, Melki R (2017) Prying into the Prion Hypothesis for Parkinson’s Disease. J Neurosci 37(41):9808–9818",{"doi":2394},"10.1523\u002FJNEUROSCI.1788-16.2017",{"id":18,"text":2396,"url":18,"identifiers":2397},"Gosset P, Camu W, Raoul C, Mezghrani A (2022) Prionoids in amyotrophic lateral sclerosis. Brain Commun 4(3):fcac145",{"doi":2398},"10.1093\u002Fbraincomms\u002Ffcac145",{"id":18,"text":2400,"url":18,"identifiers":2401},"Donnelly KM, Coleman CM, Fuller ML, Reed VL, Smerina D, Tomlinson DS, Pearce MMP (2022) Hunting for the cause: evidence for prion-like mechanisms in Huntington’s disease. Front Neurosci 16:946822",{"doi":2402},"10.3389\u002Ffnins.2022.946822",{"id":18,"text":2404,"url":18,"identifiers":2405},"Wang M, Li A, Sekiya M, Beckmann ND, Quan X, Schrode N, Fernando MB, Yu A, Zhu L, Cao J, Lyu L, Horgusluoglu E, Wang Q, Guo L, Wang YS, Neff R, Song WM, Wang E, Shen Q, Zhou X, Ming C, Ho SM, Vatansever S, Kaniskan HU, Jin J, Zhou MM, Ando K, Ho L, Slesinger PA, Yue Z, Zhu J, Katsel P, Gandy S, Ehrlich ME, Fossati V, Noggle S, Cai D, Haroutunian V, Iijima KM, Schadt E, Brennand KJ, Zhang B (2021) Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits. Key Regulators, Potential Therapeutics Alzheimer’s Disease, Neuron 109(2):257–272",{},{"id":18,"text":2407,"url":18,"identifiers":2408},"Mirhadi S, Tam S, Li Q, Moghal N, Pham NA, Tong J, Golbourn BJ, Krieger JR, Taylor P, Li M, Weiss J, Martins-Filho SN, Raghavan V, Mamatjan Y, Khan AA, Cabanero M, Sakashita S, Huo K, Agnihotri S, Ishizawa K, Waddell TK, Zadeh G, Yasufuku K, Liu G, Shepherd FA, Moran MF, Tsao MS (2022) Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes. Nat Commun 13(1):1811",{"doi":2409},"10.1038\u002Fs41467-022-29444-9",{"id":18,"text":2411,"url":18,"identifiers":2412},"Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Benner C, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10(1):1523",{"doi":2413},"10.1038\u002Fs41467-019-09234-6",{"id":18,"text":2415,"url":18,"identifiers":2416},"Mair P, Wilcox R (2020) Robust statistical methods in R using the WRS2 package. Behav Res Methods 52(2):464–488",{"doi":2417},"10.3758\u002Fs13428-019-01246-w",{"id":2419,"createTime":2420,"updateTime":2421,"relativeEntities":2422,"slug":2423,"properties":2424,"entityType":128,"verifyStatus":129,"verifyTime":2432,"verifyNote":131,"languages":18,"translateLanguages":18,"viewCount":19,"primaryUrl":2433,"fullTextUrl":18,"authors":2434,"publicationType":403,"publisherRelationship":2489,"citationCount":18,"citationInfo":18,"publishDate":2543,"publishYear":2544,"citationAnalyzeStatus":1007,"lastCitationAnalyze":2545,"indexDatabases":2546,"openAccess":18,"references":18,"isForceReanalyzing":462},"41bf522a-a963-4c90-8111-6e647f279b58","2024-01-10T02:13:52.788+00:00","2026-05-16T11:24:43.906+00:00",[],"Response-to-Simon-et-al-",{"title":2425,"gsPaper":2427,"references":2428,"doi":2430},{"EN":2426},"Response to Simon et al.,",{"VOID":784},{"VOID":2429},"Wei W, Keogh MJ, Wilson I et al (2017) Mitochondrial DNA point mutations and relative copy number in 1363 disease and control human brains. Acta Neuropathol Commun 5(1):13\nLin MT, Cantuti-Castelvetri I, Zheng K et al (2012) Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy body disease. Ann Neurol 71(6):850–4\nCantuti-Castelvetri I, Lin MT, Zheng K et al (2005) Somatic mitochondrial DNA mutations in single neurons and glia. Neurobiol Aging 26(10):1343–55\nSimon DK, Lin MT, Zheng L et al (2004) Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson's disease. Neurobiol Aging 25(1):71–81\nPayne BA, Wilson IJ, Yu-Wai-Man P et al (2013) Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet 22(2):384–90",{"VOID":2431},"10.1186\u002Fs40478-017-0434-8","2024-06-24T09:49:45.815+00:00","https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-017-0434-8",[2435,2450,2463,2476],{"id":2436,"sortIndex":19,"researcher":18,"roles":2437,"affiliations":2438,"properties":2447,"displayName":2449,"givenName":18,"familyName":18},"a446dec2-c245-48e2-9bf5-7dd867e75545",[139],[2439],{"id":2440,"sortIndex":19,"affiliation":2441,"properties":18},"2c6a5799-6815-4d54-9036-7d81a8d07793",{"id":2440,"createTime":18,"updateTime":18,"relativeEntities":2442,"slug":18,"properties":2443,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2446,"statistic":18},[],{"title":2444},{"VI":2445},"Department of Clinical Neurosciences and MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK",[],{"title":2448},{"VI":2449},"Wei Wei",{"id":2451,"sortIndex":94,"researcher":18,"roles":2452,"affiliations":2453,"properties":2460,"displayName":2462,"givenName":18,"familyName":18},"70d002e6-a36b-4e8e-a399-6518fddd7756",[139],[2454],{"id":2440,"sortIndex":19,"affiliation":2455,"properties":18},{"id":2440,"createTime":18,"updateTime":18,"relativeEntities":2456,"slug":18,"properties":2457,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2459,"statistic":18},[],{"title":2458},{"VI":2445},[],{"title":2461},{"VI":2462},"Michael J. Keogh",{"id":2464,"sortIndex":96,"researcher":18,"roles":2465,"affiliations":2466,"properties":2473,"displayName":2475,"givenName":18,"familyName":18},"9cbe810d-af35-4328-a49b-cfd89d742438",[139],[2467],{"id":320,"sortIndex":19,"affiliation":2468,"properties":18},{"id":320,"createTime":18,"updateTime":18,"relativeEntities":2469,"slug":18,"properties":2470,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2472,"statistic":18},[],{"title":2471},{"VI":325},[],{"title":2474},{"VI":2475},"James W. Ironside",{"id":2477,"sortIndex":101,"researcher":18,"roles":2478,"affiliations":2479,"properties":2486,"displayName":2488,"givenName":18,"familyName":18},"8612e8c8-9c8b-43df-974d-a88131fb580c",[139],[2480],{"id":2440,"sortIndex":19,"affiliation":2481,"properties":18},{"id":2440,"createTime":18,"updateTime":18,"relativeEntities":2482,"slug":18,"properties":2483,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2485,"statistic":18},[],{"title":2484},{"VI":2445},[],{"title":2487},{"VI":2488},"Patrick F. Chinnery",{"url":2433,"publisher":2490,"properties":2539},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2491,"slug":10,"properties":2492,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2495,"manageAffiliations":2508,"indexDatabases":2519,"url":91,"thumbnailPath":18,"statistic":2534,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":2493,"title":2494},{"VOID":13},{"EN":15},[2496,2500,2504],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2497,"label":2498,"description":2499,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":2501,"label":2502,"description":2503,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":2505,"label":2506,"description":2507,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[2509,2514],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":2510,"slug":18,"properties":2511,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2513,"statistic":18},[],{"title":2512},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":2515,"slug":18,"properties":2516,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2518,"statistic":18},[],{"title":2517},{"EN":52},[],[2520,2527],{"id":56,"indexDatabase":2521,"url":69,"indexYears":18,"academicFieldIds":2526,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":2522,"label":2523,"description":2524,"key":65,"publicationTags":2525,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":2528,"url":84,"indexYears":85,"academicFieldIds":2533,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":2529,"label":2530,"description":2531,"key":81,"publicationTags":2532,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":2535,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":2536,"totalCitation":102,"totalCitationByYear":2537,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":2538,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"pages":2540,"volume":2541},{"VOID":1004},{"VOID":2542},"5","2017-04-29",2017,"2026-05-16T11:24:43.905+00:00",[67,90],{"id":2548,"createTime":2549,"updateTime":2550,"relativeEntities":2551,"slug":2552,"properties":2553,"entityType":128,"verifyStatus":129,"verifyTime":2569,"verifyNote":131,"languages":2570,"translateLanguages":18,"viewCount":19,"primaryUrl":2571,"fullTextUrl":18,"authors":2572,"publicationType":403,"publisherRelationship":2656,"citationCount":19,"citationInfo":2706,"publishDate":2708,"publishYear":1379,"citationAnalyzeStatus":1007,"lastCitationAnalyze":2709,"indexDatabases":2710,"openAccess":18,"references":2711,"isForceReanalyzing":462},"74863906-8871-4a16-8117-209fa21231b9","2024-04-15T01:46:47.980+00:00","2026-05-16T02:18:35.368+00:00",[],"Tau-but-not-A%C3%9F-pathology-enhances-NMDAR-dependent-depotentiation-in-AD-mouse-models",{"mag":2554,"gsPaper":2556,"pmc":2557,"openalex":2559,"abstract":2561,"title":2563,"pm":2565,"doi":2567},{"VOID":2555},"2996676820",{"VOID":784},{"VOID":2558},"6902514",{"VOID":2560},"W2996676820",{"EN":2562},"\u003Cjats:title>Abstract\u003C\u002Fjats:title>\u003Cjats:p>Many mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11–15 months old male THY-Tau22 and APPPS1–21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.\u003C\u002Fjats:p>",{"EN":2564},"Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models",{"VOID":2566},"31815648",{"VOID":2568},"10.1186\u002Fs40478-019-0813-4","2024-06-23T21:28:51.947+00:00",[1796],"https:\u002F\u002Factaneurocomms.biomedcentral.com\u002Farticles\u002F10.1186\u002Fs40478-019-0813-4",[2573,2590,2605,2624,2641],{"id":2574,"sortIndex":19,"researcher":18,"roles":2575,"affiliations":2576,"properties":2585,"displayName":2587,"givenName":18,"familyName":18},"c05b09e9-79e7-45c6-b3f3-285de99e8ed2",[],[2577],{"id":2578,"sortIndex":19,"affiliation":2579,"properties":18},"644e5953-2cd3-4ec4-ba4b-e142f84af327",{"id":2578,"createTime":18,"updateTime":18,"relativeEntities":2580,"slug":18,"properties":2581,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2584,"statistic":18},[],{"title":2582},{"EN":2583},"Brain & Cognition, Faculty of Psychology and Educational Sciences, K.U.Leuven, Tiensestraat 102, 3000, Leuven, Belgium",[],{"title":2586,"openalex":2588},{"EN":2587},"Enrico Faldini",{"VOID":2589},"A5018515583",{"id":2591,"sortIndex":94,"researcher":18,"roles":2592,"affiliations":2593,"properties":2600,"displayName":2602,"givenName":18,"familyName":18},"d429c42e-e354-4f3b-bbb8-db3c2b025689",[],[2594],{"id":2578,"sortIndex":19,"affiliation":2595,"properties":18},{"id":2578,"createTime":18,"updateTime":18,"relativeEntities":2596,"slug":18,"properties":2597,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2599,"statistic":18},[],{"title":2598},{"EN":2583},[],{"title":2601,"openalex":2603},{"EN":2602},"Tariq Ahmed",{"VOID":2604},"A5078415336",{"id":2606,"sortIndex":96,"researcher":18,"roles":2607,"affiliations":2608,"properties":2617,"displayName":2621,"givenName":18,"familyName":18},"9bdfdcfd-76f9-472a-ad11-3783171ad211",[],[2609],{"id":2610,"sortIndex":19,"affiliation":2611,"properties":18},"89698029-0b12-4d90-8004-32c821867bd0",{"id":2610,"createTime":18,"updateTime":18,"relativeEntities":2612,"slug":18,"properties":2613,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2616,"statistic":18},[],{"title":2614},{"EN":2615},"Jean-Pierre Aubert research centre UMR-S1172, Université de Lille, Inserm, CHU-Lille, LabEx DISTALZ, Alzheimer & Tauopathies, 59045, Lille, France",[],{"orcid":2618,"title":2620,"openalex":2622},{"VOID":2619},"https:\u002F\u002Forcid.org\u002F0000-0002-6261-4230",{"EN":2621},"Luc Buée",{"VOID":2623},"A5052854817",{"id":2625,"sortIndex":101,"researcher":18,"roles":2626,"affiliations":2627,"properties":2634,"displayName":2638,"givenName":18,"familyName":18},"418c9e1a-2a64-4617-b37b-8f4fdd686cca",[],[2628],{"id":2610,"sortIndex":19,"affiliation":2629,"properties":18},{"id":2610,"createTime":18,"updateTime":18,"relativeEntities":2630,"slug":18,"properties":2631,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2633,"statistic":18},[],{"title":2632},{"EN":2615},[],{"orcid":2635,"title":2637,"openalex":2639},{"VOID":2636},"https:\u002F\u002Forcid.org\u002F0000-0001-5691-431X",{"EN":2638},"David Blum",{"VOID":2640},"A5053472629",{"id":2642,"sortIndex":100,"researcher":18,"roles":2643,"affiliations":2644,"properties":2651,"displayName":2653,"givenName":18,"familyName":18},"dce579ef-3ed3-4451-81d6-cc6923bc2dc0",[],[2645],{"id":2578,"sortIndex":19,"affiliation":2646,"properties":18},{"id":2578,"createTime":18,"updateTime":18,"relativeEntities":2647,"slug":18,"properties":2648,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2650,"statistic":18},[],{"title":2649},{"EN":2583},[],{"title":2652,"openalex":2654},{"EN":2653},"Detlef Balschun",{"VOID":2655},"A5030761711",{"url":18,"publisher":2657,"properties":18},{"id":6,"createTime":7,"updateTime":8,"relativeEntities":2658,"slug":10,"properties":2659,"entityType":16,"verifyStatus":17,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":19,"subjectFields":2662,"manageAffiliations":2675,"indexDatabases":2686,"url":91,"thumbnailPath":18,"statistic":2701,"gsStatistic":18,"type":107,"analyzePriority":18},[],{"issn":2660,"title":2661},{"VOID":13},{"EN":15},[2663,2667,2671],{"id":22,"createTime":18,"updateTime":18,"relativeEntities":2664,"label":2665,"description":2666,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":25},{},{"id":28,"createTime":18,"updateTime":18,"relativeEntities":2668,"label":2669,"description":2670,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":31},{},{"id":34,"createTime":18,"updateTime":18,"relativeEntities":2672,"label":2673,"description":2674,"parentId":18,"standard":18,"scholarHubFieldId":18},[],{"EN":37},{},[2676,2681],{"id":41,"createTime":18,"updateTime":18,"relativeEntities":2677,"slug":18,"properties":2678,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2680,"statistic":18},[],{"title":2679},{"EN":45},[],{"id":48,"createTime":18,"updateTime":18,"relativeEntities":2682,"slug":18,"properties":2683,"entityType":18,"verifyStatus":18,"verifyTime":18,"verifyNote":18,"languages":18,"translateLanguages":18,"viewCount":18,"url":18,"parentIds":2685,"statistic":18},[],{"title":2684},{"EN":52},[],[2687,2694],{"id":56,"indexDatabase":2688,"url":69,"indexYears":18,"academicFieldIds":2693,"indexDatabaseRanking":18},{"id":58,"createTime":18,"updateTime":18,"relativeEntities":2689,"label":2690,"description":2691,"key":65,"publicationTags":2692,"standard":18},[],{"EN":61,"VI":61},{"EN":63,"VI":64},[67,68],[71],{"id":73,"indexDatabase":2695,"url":84,"indexYears":85,"academicFieldIds":2700,"indexDatabaseRanking":90},{"id":75,"createTime":18,"updateTime":18,"relativeEntities":2696,"label":2697,"description":2698,"key":81,"publicationTags":2699,"standard":18},[],{"EN":78,"VI":78},{"EN":78,"VI":80},[83],[87,88,89],{"impactFactor":19,"impactFactorByYear":2702,"i10Index":96,"i10IndexLast5Year":19,"totalPublication":97,"totalPublicationByYear":2703,"totalCitation":102,"totalCitationByYear":2704,"totalCitationPerPublication":104,"totalCitationPerPublicationByYear":2705,"hindexLast5Year":96,"hindex":96},{"2014":94,"2015":95},{"2013":99,"2014":94,"2015":94,"2016":94,"2017":96,"2018":94,"2019":94,"2021":100,"2022":101},{"2013":102},{"2013":106},{"total":19,"publishYear":1379,"statisticByYear":2707},{},"2019-12-01","2026-05-16T02:18:35.367+00:00",[67,90],[2712,2716,2720,2724,2728,2732,2736,2740,2744,2748,2752,2756,2760,2764,2768,2772,2776,2780,2784,2788,2792,2796,2800,2804,2808,2812,2816,2820,2824,2827,2831,2835,2839,2843,2847,2851,2855,2859,2863,2866,2870,2874,2878,2882,2886,2890,2894,2898,2902,2906,2910,2914,2918,2922,2926,2930,2934,2938,2942,2946,2950,2954,2958,2962,2966,2970,2974,2978,2982,2986,2990,2994,2998,3002,3006,3010,3014,3018,3022,3026],{"id":18,"text":2713,"url":18,"identifiers":2714},"Abdou K, Shehata M, Choko K, Nishizono H, Matsuo M, Muramatsu S-I, Inokuchi K (2018) Synapse-specific representation of the identity of overlapping memory engrams. Science 360:1227–1231",{"doi":2715},"10.1126\u002Fscience.aat3810",{"id":18,"text":2717,"url":18,"identifiers":2718},"Ahmed T, Blum D, Burnouf S, Demeyer D, Buee-Scherrer V, D’Hooge R, Buee L, Balschun D (2015) Rescue of impaired late-phase long-term depression in a tau transgenic mouse model. Neurobiol Aging 36:730–739",{"doi":2719},"10.1016\u002Fj.neurobiolaging.2014.09.015",{"id":18,"text":2721,"url":18,"identifiers":2722},"Ashe KH, Zahs KR (2010) Probing the biology of Alzheimer’s disease in mice. Neuron 66:631–645",{"doi":2723},"10.1016\u002Fj.neuron.2010.04.031",{"id":18,"text":2725,"url":18,"identifiers":2726},"Benilova I, Karran E, De Strooper B (2012) The toxic Abeta oligomer and Alzheimer’s disease: an emperor in need of clothes. Nat Neurosci 15:349–357",{"doi":2727},"10.1038\u002Fnn.3028",{"id":18,"text":2729,"url":18,"identifiers":2730},"Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33:95–130",{"doi":2731},"10.1016\u002FS0165-0173(00)00019-9",{"id":18,"text":2733,"url":18,"identifiers":2734},"Buzsaki G, Leung LW, Vanderwolf CH (1983) Cellular bases of hippocampal EEG in the behaving rat. Brain Res 287:139–171",{"doi":2735},"10.1016\u002F0165-0173(83)90037-1",{"id":18,"text":2737,"url":18,"identifiers":2738},"Cai Z, Zhao Y, Zhao B (2012) Roles of glycogen synthase kinase 3 in Alzheimer’s disease. Curr Alzheimer Res 9:864–879",{"doi":2739},"10.2174\u002F156720512802455386",{"id":18,"text":2741,"url":18,"identifiers":2742},"Chakroborty S, Kim J, Schneider C, Jacobson C, Molgo J, Stutzmann GE (2012) Early presynaptic and postsynaptic calcium signaling abnormalities mask underlying synaptic depression in presymptomatic Alzheimer’s disease mice. J Neurosci 32:8341–8353",{"doi":2743},"10.1523\u002FJNEUROSCI.0936-12.2012",{"id":18,"text":2745,"url":18,"identifiers":2746},"Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul V, Shirao T, Aoki C, Huerta PT (2006) AMPA receptor downscaling at the onset of Alzheimer’s disease pathology in double knockin mice. Proc Natl Acad Sci U S A 103:3410–3415",{"doi":2747},"10.1073\u002Fpnas.0507313103",{"id":18,"text":2749,"url":18,"identifiers":2750},"Chen P, Gu Z, Liu W, Yan Z (2007) Glycogen synthase kinase 3 regulates N-methyl-D-aspartate receptor channel trafficking and function in cortical neurons. Mol Pharmacol 72:40–51",{"doi":2751},"10.1124\u002Fmol.107.034942",{"id":18,"text":2753,"url":18,"identifiers":2754},"Cheng L, Yin W-J, Zhang J-F, Qi J-S (2009) Amyloid beta-protein fragments 25-35 and 31-35 potentiate long-term depression in hippocampal CA1 region of rats in vivo. Synapse 63:206–214",{"doi":2755},"10.1002\u002Fsyn.20599",{"id":18,"text":2757,"url":18,"identifiers":2758},"Collingridge GL, Peineau S, Howland JG, Wang YT (2010) Long-term depression in the CNS. Nat Rev Neurosci 11:459–473",{"doi":2759},"10.1038\u002Fnrn2867",{"id":18,"text":2761,"url":18,"identifiers":2762},"D’Amelio M, Cavallucci V, Middei S, Marchetti C, Pacioni S, Ferri A, Diamantini A, De Zio D, Carrara P, Battistini L, Moreno S, Bacci A, Ammassari-Teule M, Marie H, Cecconi F (2011) Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer’s disease. Nat Neurosci 14:69–76",{"doi":2763},"10.1038\u002Fnn.2709",{"id":18,"text":2765,"url":18,"identifiers":2766},"Fedulov V, Rex CS, Simmons DA, Palmer L, Gall CM, Lynch G (2007) Evidence that long-term potentiation occurs within individual hippocampal synapses during learning. J Neurosci 27:8031–8039",{"doi":2767},"10.1523\u002FJNEUROSCI.2003-07.2007",{"id":18,"text":2769,"url":18,"identifiers":2770},"Franklin AV, King MK, Palomo V, Martinez A, McMahon LL, Jope RS (2014) Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation and cognition in fragile X mice. Biol Psychiatry 75:198–206",{"doi":2771},"10.1016\u002Fj.biopsych.2013.08.003",{"id":18,"text":2773,"url":18,"identifiers":2774},"Fujii S, Saito K, Miyakawa H, Ito K, Kato H (1991) Reversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of Guinea pig hippocampal slices. Brain Res 555:112–122",{"doi":2775},"10.1016\u002F0006-8993(91)90867-U",{"id":18,"text":2777,"url":18,"identifiers":2778},"Gengler S, Hamilton A, Holscher C (2010) Synaptic plasticity in the hippocampus of a APP\u002FPS1 mouse model of Alzheimer’s disease is impaired in old but not young mice. PLoS One 5:e9764",{"doi":2779},"10.1371\u002Fjournal.pone.0009764",{"id":18,"text":2781,"url":18,"identifiers":2782},"Hesse GW, Teyler TJ (1976) Reversible loss of hippocampal long term potentiation following electronconvulsive seizures. Nature 264:562–564",{"doi":2783},"10.1038\u002F264562a0",{"id":18,"text":2785,"url":18,"identifiers":2786},"Hoffmann NA, Dorostkar MM, Blumenstock S, Goedert M, Herms J (2013) Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice. Acta Neuropathol Commun 1:82",{"doi":2787},"10.1186\u002F2051-5960-1-82",{"id":18,"text":2789,"url":18,"identifiers":2790},"Hooper C, Markevich V, Plattner F, Killick R, Schofield E, Engel T, Hernandez F, Anderton B, Rosenblum K, Bliss T, Cooke SF, Avila J, Lucas JJ, Giese KP, Stephenson J, Lovestone S (2007) Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur J Neurosci 25:81–86",{"doi":2791},"10.1111\u002Fj.1460-9568.2006.05245.x",{"id":18,"text":2793,"url":18,"identifiers":2794},"Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK, Pitstick R, Carlson GA, Lanier LM, Yuan LL, Ashe KH, Liao D (2010) Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68:1067–1081",{"doi":2795},"10.1016\u002Fj.neuron.2010.11.030",{"id":18,"text":2797,"url":18,"identifiers":2798},"Hsu KS, Huang CC, Liang YC, Wu HM, Chen YL, Lo SW, Ho WC (2002) Alterations in the balance of protein kinase and phosphatase activities and age-related impairments of synaptic transmission and long-term potentiation. Hippocampus 12:787–802",{"doi":2799},"10.1002\u002Fhipo.10032",{"id":18,"text":2801,"url":18,"identifiers":2802},"Hu N-W, Klyubin I, Anwyl R, Rowan MJ (2009) GluN2B subunit-containing NMDA receptor antagonists prevent Abeta-mediated synaptic plasticity disruption in vivo. Proc Natl Acad Sci U S A 106:20504–20509",{"doi":2803},"10.1073\u002Fpnas.0908083106",{"id":18,"text":2805,"url":18,"identifiers":2806},"Huang CC, Hsu KS (2001) Progress in understanding the factors regulating reversibility of long-term potentiation. Rev Neurosci 12:51–68",{"doi":2807},"10.1515\u002FREVNEURO.2001.12.1.51",{"id":18,"text":2809,"url":18,"identifiers":2810},"Huang CC, Liang YC, Hsu KS (2001) Characterization of the mechanism underlying the reversal of long term potentiation by low frequency stimulation at hippocampal CA1 synapses. J Biol Chem 276:48108–48117",{"doi":2811},"10.1074\u002Fjbc.M106388200",{"id":18,"text":2813,"url":18,"identifiers":2814},"Huh S, Baek S-J, Lee K-H, Whitcomb DJ, Jo J, Choi S-M, Kim DH, Park M-S, Lee KH, Kim BC (2016) The reemergence of long-term potentiation in aged Alzheimer’s disease mouse model. Sci Rep 6:29152",{"doi":2815},"10.1038\u002Fsrep29152",{"id":18,"text":2817,"url":18,"identifiers":2818},"Jo J, Whitcomb DJ, Olsen KM, Kerrigan TL, Lo S-C, Bru-Mercier G, Dickinson B, Scullion S, Sheng M, Collingridge G, Cho K (2011) Abeta (1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3beta. Nat Neurosci 14:545–547",{"doi":2819},"10.1038\u002Fnn.2785",{"id":18,"text":2821,"url":18,"identifiers":2822},"Kessels HW, Nabavi S, Malinow R (2013) Metabotropic NMDA receptor function is required for beta-amyloid-induced synaptic depression. Proc Natl Acad Sci U S A 110:4033–4038",{"doi":2823},"10.1073\u002Fpnas.1219605110",{"id":18,"text":2825,"url":18,"identifiers":2826},"Khan SS, Bloom GS (2016) Tau: the Center of a Signaling Nexus in Alzheimer’s disease. Front Neurosci 10:31",{},{"id":18,"text":2828,"url":18,"identifiers":2829},"Kim J, Lee S, Park K, Hong I, Song B, Son G, Park H, Kim WR, Park E, Choe HK, Kim H, Lee C, Sun W, Kim K, Shin KS, Choi S (2007) Amygdala depotentiation and fear extinction. Proc Natl Acad Sci U S A 104:20955–20960",{"doi":2830},"10.1073\u002Fpnas.0710548105",{"id":18,"text":2832,"url":18,"identifiers":2833},"Kim JH, Anwyl R, Suh YH, Djamgoz MB, Rowan MJ (2001) Use-dependent effects of amyloidogenic fragments of (beta)-amyloid precursor protein on synaptic plasticity in rat hippocampus in vivo. J Neurosci 21:1327–1333",{"doi":2834},"10.1523\u002FJNEUROSCI.21-04-01327.2001",{"id":18,"text":2836,"url":18,"identifiers":2837},"Kremer A, Louis J V, Jaworski T, Van Leuven F (2011) GSK3 and Alzheimer’s Disease: Facts and Fiction…. Front Mol Neurosci 4:17",{"doi":2838},"10.3389\u002Ffnmol.2011.00017",{"id":18,"text":2840,"url":18,"identifiers":2841},"Larson J, Xiao P, Lynch G (1993) Reversal of LTP by theta frequency stimulation. Brain Res 600:97–102",{"doi":2842},"10.1016\u002F0006-8993(93)90406-D",{"id":18,"text":2844,"url":18,"identifiers":2845},"Latif-Hernandez A, Faldini E, Ahmed T, Balschun D (2016) Separate Ionotropic and metabotropic glutamate receptor functions in Depotentiation vs. LTP: a distinct role for Group1 mGluR subtypes and NMDARs. Front cell Neurosci 10:252",{"doi":2846},"10.3389\u002Ffncel.2016.00252",{"id":18,"text":2848,"url":18,"identifiers":2849},"Laurent C et al (2016) A2A adenosine receptor deletion is protective in a mouse model of Tauopathy. Mol Psychiatry 21:149",{"doi":2850},"10.1038\u002Fmp.2015.115",{"id":18,"text":2852,"url":18,"identifiers":2853},"Laurent C et al (2017) Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy. Brain 140:184–200",{"doi":2854},"10.1093\u002Fbrain\u002Faww270",{"id":18,"text":2856,"url":18,"identifiers":2857},"Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D (2009) Soluble oligomers of amyloid Beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62:788–801",{"doi":2858},"10.1016\u002Fj.neuron.2009.05.012",{"id":18,"text":2860,"url":18,"identifiers":2861},"Liu L, Wong TP, Pozza MF, Lingenhoehl K, Wang Y, Sheng M, Auberson YP, Wang YT (2004) Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science (80- ) 304:1021–1024",{"doi":2862},"10.1126\u002Fscience.1096615",{"id":18,"text":2864,"url":18,"identifiers":2865},"Llorens-Martin M, Jurado J, Hernandez F, Avila J (2014) GSK-3beta, a pivotal kinase in Alzheimer disease. Front Mol Neurosci 7:46",{},{"id":18,"text":2867,"url":18,"identifiers":2868},"Lo AC, Iscru E, Blum D, Tesseur I, Callaerts-Vegh Z, Buee L, De Strooper B, Balschun D, D’Hooge R (2013a) Amyloid and tau neuropathology differentially affect prefrontal synaptic plasticity and cognitive performance in mouse models of Alzheimer’s disease. J Alzheimers Dis 37:109–125",{"doi":2869},"10.3233\u002FJAD-122296",{"id":18,"text":2871,"url":18,"identifiers":2872},"Lo AC, Tesseur I, Scopes DI, Nerou E, Callaerts-Vegh Z, Vermaercke B, Treherne JM, De Strooper B, D’Hooge R (2013b) Dose-dependent improvements in learning and memory deficits in APPPS1-21 transgenic mice treated with the orally active Abeta toxicity inhibitor SEN1500. Neuropharmacology 75:458–466",{"doi":2873},"10.1016\u002Fj.neuropharm.2013.08.030",{"id":18,"text":2875,"url":18,"identifiers":2876},"Mandelkow EM, Stamer K, Vogel R, Thies E, Mandelkow E (2003) Clogging of axons by tau, inhibition of axonal traffic and starvation of synapses. Neurobiol Aging 24:1079–1085",{"doi":2877},"10.1016\u002Fj.neurobiolaging.2003.04.007",{"id":18,"text":2879,"url":18,"identifiers":2880},"Marchetti C, Marie H (2011) Hippocampal synaptic plasticity in Alzheimer’s disease: what have we learned so far from transgenic models? Rev Neurosci 22:373–402",{"doi":2881},"10.1515\u002Frns.2011.035",{"id":18,"text":2883,"url":18,"identifiers":2884},"Marciniak E et al (2017) Tau deletion promotes brain insulin resistance. J Exp Med 214:2257–2269",{"doi":2885},"10.1084\u002Fjem.20161731",{"id":18,"text":2887,"url":18,"identifiers":2888},"Martin SJ, Grimwood PD, Morris RG (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu Rev Neurosci 23:649–711",{"doi":2889},"10.1146\u002Fannurev.neuro.23.1.649",{"id":18,"text":2891,"url":18,"identifiers":2892},"Massey PV, Johnson BE, Moult PR, Auberson YP, Brown MW, Molnar E, Collingridge GL, Bashir ZI (2004) Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression. J Neurosci 24:7821–7828",{"doi":2893},"10.1523\u002FJNEUROSCI.1697-04.2004",{"id":18,"text":2895,"url":18,"identifiers":2896},"Migues PV, Liu L, Archbold GEB, Einarsson EO, Wong J, Bonasia K, Ko SH, Wang YT, Hardt O (2016) Blocking synaptic removal of GluA2-containing AMPA receptors prevents the natural forgetting of long-term memories. J Neurosci 36:3481–3494",{"doi":2897},"10.1523\u002FJNEUROSCI.3333-15.2016",{"id":18,"text":2899,"url":18,"identifiers":2900},"Milner AJ, Cummings DM, Spencer JP, Murphy KP (2004) Bi-directional plasticity and age-dependent long-term depression at mouse CA3-CA1 hippocampal synapses. Neurosci Lett 367:1–5",{"doi":2901},"10.1016\u002Fj.neulet.2004.04.056",{"id":18,"text":2903,"url":18,"identifiers":2904},"Nabavi S, Kessels HW, Alfonso S, Aow J, Fox R, Malinow R (2013) Metabotropic NMDA receptor function is required for NMDA receptor-dependent long-term depression. Proc Natl Acad Sci U S A 110:4027–4032",{"doi":2905},"10.1073\u002Fpnas.1219454110",{"id":18,"text":2907,"url":18,"identifiers":2908},"Nelson PT et al (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362–381",{"doi":2909},"10.1097\u002FNEN.0b013e31825018f7",{"id":18,"text":2911,"url":18,"identifiers":2912},"Nicoll RA (2017) A brief history of long-term potentiation. Neuron 93:281–290",{"doi":2913},"10.1016\u002Fj.neuron.2016.12.015",{"id":18,"text":2915,"url":18,"identifiers":2916},"Norris CM, Korol DL, Foster TC (1996) Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging. J Neurosci 16:5382–5392",{"doi":2917},"10.1523\u002FJNEUROSCI.16-17-05382.1996",{"id":18,"text":2919,"url":18,"identifiers":2920},"O’Dell TJ, Kandel ER (1994) Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases. Learn Mem 1:129–139",{"doi":2921},"10.1101\u002Flm.1.2.129",{"id":18,"text":2923,"url":18,"identifiers":2924},"Peineau S, Bradley C, Taghibiglou C, Doherty A, Bortolotto ZA, Wang YT, Collingridge GL (2008) The role of GSK-3 in synaptic plasticity. Br J Pharmacol 153(Suppl):S428–S437",{"doi":2925},"10.1038\u002Fbjp.2008.2",{"id":18,"text":2927,"url":18,"identifiers":2928},"Peineau S, Taghibiglou C, Bradley C, Wong TP, Liu L, Lu J, Lo E, Wu D, Saule E, Bouschet T, Matthews P, Isaac JT, Bortolotto ZA, Wang YT, Collingridge GL (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3beta. Neuron 53:703–717",{"doi":2929},"10.1016\u002Fj.neuron.2007.01.029",{"id":18,"text":2931,"url":18,"identifiers":2932},"Priller C, Mitteregger G, Paluch S, Vassallo N, Staufenbiel M, Kretzschmar HA, Jucker M, Herms J (2009) Excitatory synaptic transmission is depressed in cultured hippocampal neurons of APP\u002FPS1 mice. Neurobiol Aging 30:1227–1237",{"doi":2933},"10.1016\u002Fj.neurobiolaging.2007.10.016",{"id":18,"text":2935,"url":18,"identifiers":2936},"Qi Y, Klyubin I, Hu N-W, Ondrejcak T, Rowan MJ (2019) Pre-plaque ass-mediated impairment of synaptic Depotentiation in a transgenic rat model of Alzheimer’s disease amyloidosis. Front Neurosci 13:861",{"doi":2937},"10.3389\u002Ffnins.2019.00861",{"id":18,"text":2939,"url":18,"identifiers":2940},"Radde R, Bolmont T, Kaeser SA, Coomaraswamy J, Lindau D, Stoltze L, Calhoun ME, Jaggi F, Wolburg H, Gengler S, Haass C, Ghetti B, Czech C, Holscher C, Mathews PM, Jucker M (2006) Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep 7:940–946",{"doi":2941},"10.1038\u002Fsj.embor.7400784",{"id":18,"text":2943,"url":18,"identifiers":2944},"Ronicke R, Mikhaylova M, Ronicke S, Meinhardt J, Schroder UH, Fandrich M, Reiser G, Kreutz MR, Reymann KG (2011) Early neuronal dysfunction by amyloid beta oligomers depends on activation of NR2B-containing NMDA receptors. Neurobiol Aging 32:2219–2228",{"doi":2945},"10.1016\u002Fj.neurobiolaging.2010.01.011",{"id":18,"text":2947,"url":18,"identifiers":2948},"Rupp NJ, Wegenast-Braun BM, Radde R, Calhoun ME, Jucker M (2011) Early onset amyloid lesions lead to severe neuritic abnormalities and local, but not global neuron loss in APPPS1 transgenic mice. Neurobiol aging 32:2324.e1-6",{"doi":2949},"10.1016\u002Fj.neurobiolaging.2010.08.014",{"id":18,"text":2951,"url":18,"identifiers":2952},"Sanderson TM (2012) Molecular mechanisms involved in depotentiation and their relevance to schizophrenia. Chonnam Med J 48:1–6",{"doi":2953},"10.4068\u002Fcmj.2012.48.1.1",{"id":18,"text":2955,"url":18,"identifiers":2956},"Sasaguri H, Nilsson P, Hashimoto S, Nagata K, Saito T, De Strooper B, Hardy J, Vassar R, Winblad B, Saido TC (2017) APP mouse models for Alzheimer’s disease preclinical studies. EMBO J 36:2473–2487",{"doi":2957},"10.15252\u002Fembj.201797397",{"id":18,"text":2959,"url":18,"identifiers":2960},"Schindowski K, Bretteville A, Leroy K, Begard S, Brion JP, Hamdane M, Buee L (2006) Alzheimer’s disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol 169:599–616",{"doi":2961},"10.2353\u002Fajpath.2006.060002",{"id":18,"text":2963,"url":18,"identifiers":2964},"Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81:741–766",{"doi":2965},"10.1152\u002Fphysrev.2001.81.2.741",{"id":18,"text":2967,"url":18,"identifiers":2968},"Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science (80- ) 298:789–791",{"doi":2969},"10.1126\u002Fscience.1074069",{"id":18,"text":2971,"url":18,"identifiers":2972},"Sheng M, Sabatini BL, Sudhof TC (2012) Synapses and Alzheimer’s disease. Cold Spring Harb Perspect Biol 4",{"doi":2973},"10.1101\u002Fcshperspect.a005777",{"id":18,"text":2975,"url":18,"identifiers":2976},"Shipton OA, Leitz JR, Dworzak J, Acton CEJ, Tunbridge EM, Denk F, Dawson HN, Vitek MP, Wade-Martins R, Paulsen O, Vargas-Caballero M (2011) Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. J Neurosci 31:1688–1692",{"doi":2977},"10.1523\u002FJNEUROSCI.2610-10.2011",{"id":18,"text":2979,"url":18,"identifiers":2980},"Song S, Wang X, Sava V, Weeber EJ, Sanchez-Ramos J (2014) In vivo administration of granulocyte colony-stimulating factor restores long-term depression in hippocampal slices prepared from transgenic APP\u002FPS1 mice. J Neurosci Res 92:975–980",{"doi":2981},"10.1002\u002Fjnr.23378",{"id":18,"text":2983,"url":18,"identifiers":2984},"Sri S, Pegasiou C-M, Cave CA, Hough K, Wood N, Gomez-Nicola D, Deinhardt K, Bannerman D, Perry VH, Vargas-Caballero M (2019) Emergence of synaptic and cognitive impairment in a mature-onset APP mouse model of Alzheimer’s disease. Acta Neuropathol Commun 7:25",{"doi":2985},"10.1186\u002Fs40478-019-0670-1",{"id":18,"text":2987,"url":18,"identifiers":2988},"Staubli U, Lynch G (1990) Stable depression of potentiated synaptic responses in the hippocampus with 1-5 Hz stimulation. Brain Res 513:113–118",{"doi":2989},"10.1016\u002F0006-8993(90)91096-Y",{"id":18,"text":2991,"url":18,"identifiers":2992},"Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O, Drexler D, Zhou L, Rune G, Mandelkow E, D’Hooge R, Alzheimer C, Mandelkow E-M (2011) Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic tau mutant. J Neurosci 31:2511–2525",{"doi":2993},"10.1523\u002FJNEUROSCI.5245-10.2011",{"id":18,"text":2995,"url":18,"identifiers":2996},"Takashima A, Noguchi K, Michel G, Mercken M, Hoshi M, Ishiguro K, Imahori K (1996) Exposure of rat hippocampal neurons to amyloid beta peptide (25-35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I\u002Fglycogen synthase kinase-3 beta. Neurosci Lett 203:33–36",{"doi":2997},"10.1016\u002F0304-3940(95)12257-5",{"id":18,"text":2999,"url":18,"identifiers":3000},"Van der Jeugd A, Ahmed T, Burnouf S, Belarbi K, Hamdame M, Grosjean ME, Humez S, Balschun D, Blum D, Buee L, D’Hooge R (2011) Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. Neurobiol Learn Mem 95:296–304",{"doi":3001},"10.1016\u002Fj.nlm.2010.12.005",{"id":18,"text":3003,"url":18,"identifiers":3004},"Villarreal DM, Do V, Haddad E, Derrick BE (2002) NMDA receptor antagonists sustain LTP and spatial memory: active processes mediate LTP decay. Nat Neurosci 5:48–52",{"doi":3005},"10.1038\u002Fnn776",{"id":18,"text":3007,"url":18,"identifiers":3008},"Wagner JJ, Alger BE (1995) GABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus. J Neurosci 15:1577–1586",{"doi":3009},"10.1523\u002FJNEUROSCI.15-02-01577.1995",{"id":18,"text":3011,"url":18,"identifiers":3012},"Waldron A-M, Wintmolders C, Bottelbergs A, Kelley JB, Schmidt ME, Stroobants S, Langlois X, Staelens S (2015) In vivo molecular neuroimaging of glucose utilization and its association with fibrillar amyloid-beta load in aged APPPS1-21 mice. Alzheimers Res Ther 7:76",{"doi":3013},"10.1186\u002Fs13195-015-0158-6",{"id":18,"text":3015,"url":18,"identifiers":3016},"Whitlock JR, Heynen AJ, Shuler MG, Bear MF (2006) Learning induces long-term potentiation in the hippocampus. Science (80- ) 313:1093–1097",{"doi":3017},"10.1126\u002Fscience.1128134",{"id":18,"text":3019,"url":18,"identifiers":3020},"Xu L, Anwyl R, Rowan MJ (1998) Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus. Nature 394:891–894",{"doi":3021},"10.1038\u002F29783",{"id":18,"text":3023,"url":18,"identifiers":3024},"Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337–351",{"doi":3025},"10.1016\u002Fj.neuron.2007.01.010",{"id":18,"text":3027,"url":18,"identifiers":3028},"Zhu Y, Pak D, Qin Y, McCormack SG, Kim MJ, Baumgart JP, Velamoor V, Auberson YP, Osten P, van Aelst L, Sheng M, Zhu JJ (2005) Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron 46:905–916",{"doi":3029},"10.1016\u002Fj.neuron.2005.04.037"]