Locus coeruleus cellular and molecular pathology during the progression of Alzheimer’s disease
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Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979) Changes in the brain catecholamines in patients with dementia of Alzheimer type. Br J Psychiatry 135:216–223
Albert MS, Dekosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:270–279
Alldred MJ, Che S, Ginsberg SD (2009) Terminal continuation (TC) RNA amplification without second strand synthesis. J Neurosci Methods 177:381–385
Alldred MJ, Duff KE, Ginsberg SD (2012) Microarray analysis of CA1 pyramidal neurons in a mouse model of tauopathy reveals progressive synaptic dysfunction. Neurobiol Dis 45:751–762
Arendt T (2000) Alzheimer’s disease as a loss of differentiation control in a subset of neurons that retain immature features in the adult brain. Neurobiol Aging 21:783–796
Arendt T, Bruckner MK, Bigl V, Marcova L (1995) Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer’s disease. III. The basal forebrain compared with other subcortical areas. J Comp Neurol 351:223–246
Arendt T, Bruckner MK, Morawski M, Jager C, Gertz HJ (2015) Early neurone loss in Alzheimer’s disease: cortical or subcortical? Acta Neuropathol Commun 3:10. doi: 10.1186/s40478-015-0187-1
Arendt T, Schindler C, Bruckner MK, Eschrich K, Bigl V, Zedlick D, Marcova L (1997) Plastic neuronal remodeling is impaired in patients with Alzheimer’s disease carrying apolipoprotein epsilon 4 allele. J Neurosci 17:516–529
Arnold SE, Louneva N, Cao K, Wang LS, Han LY, Wolk DA, Negash S, Leurgans SE, Schneider JA, Buchman AS, Wilson RS, Bennett DA (2012) Cellular, synaptic, and biochemical features of resilient cognition in Alzheimer’s disease. Neurobiol Aging 34:157–168
Arnsten AF, Goldman-Rakic PS (1984) Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey. Brain Res 306:9–18
Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403–450
Beck JS, Mufson EJ, Counts SE (2015) Evidence for mitochondrial UPR gene activation in familial and sporadic Alzheimer’s disease. Curr Alzheimer Res 13:610–614.
Bennett DA, Schneider JA, Bienias JL, Evans DA, Wilson RS (2005) Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions. Neurology 64:834–841
Bennett DA, Wilson RS, Schneider JA, Evans DA, Beckett LA, Aggarwal NT, Barnes LL, Fox JH, Bach J (2002) Natural history of mild cognitive impairment in older persons. Neurology 59:198–205
Berchtold NC, Sabbagh MN, Beach TG, Kim RC, Cribbs DH, Cotman CW (2014) Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer’s disease. Neurobiol Aging 35:1961–1972
Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33–84
Biswas M, Chan JY (2010) Role of Nrf1 in antioxidant response element-mediated gene expression and beyond. Toxicol Appl Pharmacol 244:16–20
Bondareff W, Mountjoy CQ, Roth M, Rossor MN, Iversen LL, Reynolds GP, Hauser DL (1987) Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease. Alzheimer Dis Assoc Disord 1:256–262
Bondareff W, Mountjoy CQ, Roth M (1981) Selective loss of neurones of origin of adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Lancet 1:783–784
Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259
Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol 121:171–181
Buettner F, Natarajan KN, Casale FP, Proserpio V, Scialdone A, Theis FJ, Teichmann SA, Marioni JC, Stegle O (2015) Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells. Nat Biotechnol 33:155–160
Busch C, Bohl J, Ohm TG (1997) Spatial, temporal and numeric analysis of Alzheimer changes in the nucleus coeruleus. Neurobiol Aging 18:401–406
Chan-Palay V, Asan E (1989) Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson’s disease with and without dementia and depression. J Comp Neurol 287:373–392
Chan-Palay V, Asan E (1989) Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression. J Comp Neurol 287:357–372
Che S, Ginsberg SD (2004) Amplification of RNA transcripts using terminal continuation. Lab Invest 84:131–137
Counts SE, Alldred MJ, Che S, Ginsberg SD, Mufson EJ (2013) Synaptic gene dysregulation within hippocampal CA1 pyramidal neurons in mild cognitive impairment. Neuropharmacology 79C:172–179.
Counts SE, He B, Che S, Ginsberg SD, Mufson EJ (2008) Galanin hyperinnervation upregulates choline acetyltransferase expression in cholinergic basal forebrain neurons in Alzheimer’s disease. Neurodegener Dis 5:228–231.
Counts SE, He B, Che S, Ginsberg SD, Mufson EJ (2009) Galanin fiber hyperinnervation preserves neuroprotective gene expression in cholinergic basal forebrain neurons in Alzheimer’s disease. J Alzheimers Dis 18:885–896
Counts SE, Chen EY, Che S, Ikonomovic MD, Wuu J, Ginsberg SD, Dekosky ST, Mufson EJ (2006) Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer’s disease. Dement Geriatr Cogn Disord 21:205–214.
Counts SE, He B, Che S, Ikonomovic MD, DeKosky ST, Ginsberg SD, Mufson EJ (2007) Alpha7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in Alzheimer disease. Arch Neurol 64:1771–1776
Counts SE, Mufson EJ (2010) Noradrenaline activation of neurotrophic pathways protects against neuronal amyloid toxicity. J Neurochem 113:649–660
Counts SE, Mufson EJ (2012) Locus coeruleus. In: Mai JK, Paxinos G (eds) The human nervous system, 3rd edn. Academic, London, pp 425–438
Counts SE, Nadeem M, Lad SP, Wuu J, Mufson EJ (2006) Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment. J Neuropathol Exp Neurol 65:592–601
Dahlstroem A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl:SUPPL 232:231–255
Davies P, Maloney AJ (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2:1403
de Silva R, Lashley T, Gibb G, Hanger D, Hope A, Reid A, Bandopadhyay R, Utton M, Strand C, Jowett T, Khan N, Anderton B, Wood N, Holton J, Revesz T, Lees A (2003) Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol Appl Neurobiol 29:288–302
Deconinck AE, Potter AC, Tinsley JM, Wood SJ, Vater R, Young C, Metzinger L, Vincent A, Slater CR, Davies KE (1997) Postsynaptic abnormalities at the neuromuscular junctions of utrophin-deficient mice. J Cell Biol 136:883–894
Deller T, Korte M, Chabanis S, Drakew A, Schwegler H, Stefani GG, Zuniga A, Schwarz K, Bonhoeffer T, Zeller R, Frotscher M, Mundel P (2003) Synaptopodin-deficient mice lack a spine apparatus and show deficits in synaptic plasticity. Proc Natl Acad Sci U S A 100:10494–10499
Dhar SS, Liang HL, Wong-Riley MT (2009) Nuclear respiratory factor 1 co-regulates AMPA glutamate receptor subunit 2 and cytochrome c oxidase: tight coupling of glutamatergic transmission and energy metabolism in neurons. J Neurochem 108:1595–1606
Dhar SS, Ongwijitwat S, Wong-Riley MT (2008) Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of cytochrome c oxidase in neurons. J Biol Chem 283:3120–3129
Elder GA, Friedrich VL Jr, Kang C, Bosco P, Gourov A, Tu PH, Zhang B, Lee VM, Lazzarini RA (1998) Requirement of heavy neurofilament subunit in the development of axons with large calibers. J Cell Biol 143:195–205
Feinstein DL, Heneka MT, Gavrilyuk V, Dello Russo C, Weinberg G, Galea E (2002) Noradrenergic regulation of inflammatory gene expression in brain. Neurochem Int 41:357–365
Feinstein DL, Kalinin S, Braun D (2016) Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system. J Neurochem 139(Suppl 2):154–178
Foote SL (1997) The primate locus coeruleus: the chemcial neuroanatomy of the nucleus, its efferent projection, and its target receptors. In: Bloom FE, Bjorklund A, Hokfelt T (eds) Handbook of chemical neuroanatomy, vol 13. Elsevier, Amsterdam, pp 187–210
Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63:844–914
Fornuskova D, Stiburek L, Wenchich L, Vinsova K, Hansikova H, Zeman J (2010) Novel insights into the assembly and function of human nuclear-encoded cytochrome c oxidase subunits 4, 5a, 6a, 7a and 7b. Biochem J 428:363–374
Forstl H, Levy R, Burns A, Luthert P, Cairns N (1994) Disproportionate loss of noradrenergic and cholinergic neurons as cause of depression in Alzheimer’s disease--a hypothesis. Pharmacopsychiatry 27:11–15
German DC, Manaye KF, White CL 3rd, Woodward DJ, McIntire DD, Smith WK, Kalaria RN, Mann DM (1992) Disease-specific patterns of locus coeruleus cell loss. Ann Neurol 32:667–676
German DC, Walker BS, Manaye K, Smith WK, Woodward DJ, North AJ (1988) The human locus coeruleus: computer reconstruction of cellular distribution. J Neurosci 8:1776–1788
German DC, White CL 3rd, Sparkman DR (1987) Alzheimer’s disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience 21:305–312
Ginsberg SD, Alldred MJ, Counts SE, Cataldo AM, Neve RL, Jiang Y, Wuu J, Chao MV, Mufson EJ, Nixon RA, Che S (2010) Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer’s disease progression. Biol Psychiatry 68:885–893
Ginsberg SD, Che S, Counts SE, Mufson EJ (2006) Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer’s disease. J Neurochem 96:1401–1408
Grudzien A, Shaw P, Weintraub S, Bigio E, Mash DC, Mesulam MM (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer’s disease. Neurobiol Aging 28:327–335
Gundersen HJ, Bendtsen TF, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A et al (1988) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. Apmis 96:379–394
Haglund M, Friberg N, Danielsson EJ, Norrman J, Englund E (2016) A methodological study of locus coeruleus degeneration in dementing disorders. Clin Neuropathol 35:287–294
Heneka MT, Galea E, Gavriluyk V, Dumitrescu-Ozimek L, Daeschner J, O’Banion MK, Weinberg G, Klockgether T, Feinstein DL (2002) Noradrenergic depletion potentiates beta -amyloid-induced cortical inflammation: implications for Alzheimer’s disease. J Neurosci 22:2434–2442
Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21:3017–3023
Hue L, Rider MH (1987) Role of fructose 2,6-bisphosphate in the control of glycolysis in mammalian tissues. Biochem J 245:313–324
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Thies B, Trojanowski JQ, Vinters HV, Montine TJ (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 8:1–13
Ishizawa T, Mattila P, Davies P, Wang D, Dickson DW (2003) Colocalization of tau and alpha-synuclein epitopes in Lewy bodies. J Neuropathol Exp Neurol 62:389–397
Jacobs HI, Wiese S, van de Ven V, Gronenschild EH, Verhey FR, Matthews PM (2015) Relevance of parahippocampal-locus coeruleus connectivity to memory in early dementia. Neurobiol Aging 36:618–626
Kalinin S, Polak PE, Lin SX, Sakharkar AJ, Pandey SC, Feinstein DL (2012) The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer’s disease. Neurobiol Aging 33:1651–1663
Kemper CM, O’Connor DT, Westlund KN (1987) Immunocytochemical localization of dopamine-beta-hydroxylase in neurons of the human brain stem. Neuroscience 23:981–989
Kim T, Lim CS, Kaang BK (2015) Cell type-specific gene expression profiling in brain tissue: comparison between TRAP, LCM and RNA-seq. BMB Rep 48:388–394
Kordower JH, Chu Y, Stebbins GT, DeKosky ST, Cochran EJ, Bennett D, Mufson EJ (2001) Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann Neurol 49:202–213
Kremerskothen J, Plaas C, Kindler S, Frotscher M, Barnekow A (2005) Synaptopodin, a molecule involved in the formation of the dendritic spine apparatus, is a dual actin/alpha-actinin binding protein. J Neurochem 92:597–606
Levy SF, Leboeuf AC, Massie MR, Jordan MA, Wilson L, Feinstein SC (2005) Three- and four-repeat tau regulate the dynamic instability of two distinct microtubule subpopulations in qualitatively different manners. Implications for neurodegeneration. J Biol Chem 280:13520–13528
Liang WS, Dunckley T, Beach TG, Grover A, Mastroeni D, Ramsey K, Caselli RJ, Kukull WA, McKeel D, Morris JC, Hulette CM, Schmechel D, Reiman EM, Rogers J, Stephan DA (2010) Neuronal gene expression in non-demented individuals with intermediate Alzheimer’s Disease neuropathology. Neurobiol Aging 31:549–566
Liang WS, Reiman EM, Valla J, Dunckley T, Beach TG, Grover A, Niedzielko TL, Schneider LE, Mastroeni D, Caselli R, Kukull W, Morris JC, Hulette CM, Schmechel D, Rogers J, Stephan DA (2008) Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci U S A 105:4441–4446
Liu X, Ye K, Weinshenker D (2015) Norepinephrine Protects against Amyloid-beta Toxicity via TrkB. J Alzheimers Dis 44:251–260
Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA (2015) Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:1202–1214
Madrigal JL, Kalinin S, Richardson JC, Feinstein DL (2007) Neuroprotective actions of noradrenaline: effects on glutathione synthesis and activation of peroxisome proliferator activated receptor delta. J Neurochem 103:2092–2101
Mann DM, Lincoln J, Yates PO, Stamp JE, Toper S (1980) Changes in the monoamine containing neurones of the human CNS in senile dementia. Br J Psychiatry 136:533–541
Mann DM, Yates PO, Marcyniuk B (1984) A comparison of changes in the nucleus basalis and locus caeruleus in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 47:201–203
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR (2006) Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63:38–46
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944
Mesulam MM (1999) Neuroplasticity failure in Alzheimer’s disease: bridging the gap between plaques and tangles. Neuron 24:521–529
Metin C, Deleglise D, Serafini T, Kennedy TE, Tessier-Lavigne M (1997) A role for netrin-1 in the guidance of cortical efferents. Development 124:5063–5074
Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41:479–486
Mitew S, Kirkcaldie MT, Dickson TC, Vickers JC (2013) Neurites containing the neurofilament-triplet proteins are selectively vulnerable to cytoskeletal pathology in Alzheimer’s disease and transgenic mouse models. Front Neuroanat 7:30
Morrison JH, Foote SL, O’Connor D, Bloom FE (1982) Laminar, tangential and regional organization of the noradrenergic innervation of monkey cortex: dopamine-beta-hydroxylase immunohistochemistry. Brain Res Bull 9:309–319
Morrison JH, Molliver ME, Grzanna R (1979) Noradrenergic innervation of cerebral cortex: widespread effects of local cortical lesions. Science 205:313–316
Mufson EJ, Bothwell M, Kordower JH (1989) Loss of nerve growth factor receptor-containing neurons in Alzheimer’s disease: a quantitative analysis across subregions of the basal forebrain. Exp Neurol 105:221–232
Mufson EJ, Chen EY, Cochran EJ, Beckett LA, Bennett DA, Kordower JH (1999) Entorhinal cortex beta-amyloid load in individuals with mild cognitive impairment. Exp Neurol 158:469–490
Mufson EJ, Binder LI, Counts SE, DeKosky ST, de Toledo-Morrell L, Ginsberg SD, Ikonomovic MD, Perez SE, Scheff, SW (2012) Mild cognitive impairment: pathology and mechanisms. Acta Neuropathol 123:13–30
Mufson EJ, Ikonomovic MD, Counts SE, Perez SE, Malek-Ahmadi M, Scheff SW, Ginsberg SD (2016) Molecular and cellular pathophysiology of preclinical Alzheimer’s disease. Behav Brain Res 311:54–690
Mufson EJ, Ma SY, Cochran EJ, Bennett DA, Beckett LA, Jaffar S, Saragovi HU, Kordower JH (2000) Loss of nucleus basalis neurons containing trkA immunoreactivity in individuals with mild cognitive impairment and early Alzheimer’s disease. J Comp Neurol 427:19–30
Mufson EJ, Ma SY, Dills J, Cochran EJ, Leurgans S, Wuu J, Bennett DA, Jaffar S, Gilmor ML, Levey AI, Kordower JH (2002) Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer’s disease. J Comp Neurol 443:136–153
Nixon RA, Saito KI, Grynspan F, Griffin WR, Katayama S, Honda T, Mohan PS, Shea TB, Beermann M (1994) Calcium-activated neutral proteinase (calpain) system in aging and Alzheimer’s disease. Ann N Y Acad Sci 747:77–91
Ohm TG, Busch C, Bohl J (1997) Unbiased estimation of neuronal numbers in the human nucleus coeruleus during aging. Neurobiol Aging 18:393–399
Palmer AM, Wilcock GK, Esiri MM, Francis PT, Bowen DM (1987) Monoaminergic innervation of the frontal and temporal lobes in Alzheimer’s disease. Brain Res 401:231–238
Perez SE, He B, Nadeem M, Wuu J, Scheff SW, Abrahamson EE, Ikonomovic MD, Mufson EJ (2015) Resilience of precuneus neurotrophic signaling pathways despite amyloid pathology in prodromal Alzheimer’s disease. Biol Psychiatry 77:693–703
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, Ritchie K, Rossor M, Thal L, Winblad B (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992
Phillips C, Fahimi A, Das D, Mojabi FS, Ponnusamy R, Salehi A (2016) Noradrenergic system in down syndrome and Alzheimer’s disease a target for therapy. Curr Alzheimer Res 13:68–83
Price JL, Amaral DG (1981) An autoradiographic study of the projections of the central nucleus of the monkey amygdala. J Neurosci 1:1242–1259
Price JL, Morris JC (1999) Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 45:358–368
Reddy PH (2011) Abnormal tau, mitochondrial dysfunction, impaired axonal transport of mitochondria, and synaptic deprivation in Alzheimer’s disease. Brain Res 1415:136–148
Reddy PH, Tripathi R, Troung Q, Tirumala K, Reddy TP, Anekonda V, Shirendeb UP, Calkins MJ, Reddy AP, Mao P, Manczak M (2012) Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer’s disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim Biophys Acta 1822:639–649
Reiner A, Yekutieli D, Benjamini Y (2003) Identifying differentially expressed genes using false discovery rate controlling procedures. Bioinformatics 19:368–375
Riascos D, Nicholas A, Samaeekia R, Yukhananov R, Mesulam MM, Bigio EH, Weintraub S, Guo L, Geula C (2014) Alterations of Ca(2)(+)-responsive proteins within cholinergic neurons in aging and Alzheimer’s disease. Neurobiol Aging 35:1325–1333
Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10:211–223
Schneider JA, Bienias JL, Gilley DW, Kvarnberg DE, Mufson EJ, Bennett DA (2002) Improved detection of substantia nigra pathology in Alzheimer’s disease. J Histochem Cytochem 50:99–106
Schoch KM, DeVos SL, Miller RL, Chun SJ, Norrbom M, Wozniak DF, Dawson HN, Bennett CF, Rigo F, Miller TM (2016) Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model. Neuron 90:941–947
Simic G, Babic Leko M, Wray S, Harrington CR, Delalle I, Jovanov-Milosevic N, Bazadona D, Buee L, de Silva R, Di Giovanni G, Wischik CM, Hof PR (2016) Monoaminergic neuropathology in Alzheimer’s disease. Prog Neurobiol. doi: 10.1016/j.pneurobio.2016.04.001
Su B, Wang X, Nunomura A, Moreira PI, Lee HG, Perry G, Smith MA, Zhu X (2008) Oxidative stress signaling in Alzheimer’s disease. Curr Alzheimer Res 5:525–532
Theofilas P, Ehrenberg AJ, Dunlop S, Di Lorenzo Alho AT, Nguy A, Leite RE, Rodriguez RD, Mejia MB, Suemoto CK, Ferretti-Rebustini RE, Polichiso L, Nascimento CF, Seeley WW, Nitrini R, Pasqualucci CA, Jacob Filho W, Rueb U, Neuhaus J, Heinsen H, Grinberg LT (2016) Locus coeruleus volume and cell population changes during Alzheimer’s disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery. Alzheimers Dement. doi: 10.1016/j.jalz.2016.06.2362
Tiernan CT, Ginsberg SD, Guillozet-Bongaarts AL, Ward SM, He B, Kanaan NM, Mufson EJ, Binder LI, Counts SE (2016) Protein homeostasis gene dysregulation in pretangle bearing nucleus basalis neurons during the progression of Alzheimer’s disease. Neurobiol Aging 42:80–90
Tomonaga M (1983) Neuropathology of the locus ceruleus: a semi-quantitative study. J Neurol 230:231–240
Trumpower BL (1981) Function of the iron-sulfur protein of the cytochrome b-c1 segment in electron-transfer and energy-conserving reactions of the mitochondrial respiratory chain. Biochim Biophys Acta 639:129–155
Tymanskyj SR, Scales TM, Gordon-Weeks PR (2012) MAP1B enhances microtubule assembly rates and axon extension rates in developing neurons. Mol Cell Neurosci 49:110–119
Unnerstall JR, Kopajtic TA, Kuhar MJ (1984) Distribution of alpha 2 agonist binding sites in the rat and human central nervous system: analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents. Brain Res 319:69–101
Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA (2005) Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. J Neurochem 93:953–962
Weinshenker D (2008) Functional consequences of locus coeruleus degeneration in Alzheimer’s disease. Curr Alzheimer Res 5:342–345
West MJ (1993) Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 14:287–293
Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10:122–126
Wilson RS, Nag S, Boyle PA, Hizel LP, Yu L, Buchman AS, Schneider JA, Bennett DA (2013) Neural Reserve, Neuronal Density in the Locus Coeruleus, and Cognitive Decline. Neurology 80:1202–1208
Winblad B, Palmer K, Kivipelto M, Jelic V, Fratiglioni L, Wahlund LO, Nordberg A, Backman L, Albert M, Almkvist O, Arai H, Basun H, Blennow K, de Leon M, DeCarli C, Erkinjuntti T, Giacobini E, Graff C, Hardy J, Jack C, Jorm A, Ritchie K, van Duijn C, Visser P, Petersen RC (2004) Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. J Intern Med 256:240–246
Yaffe K, Petersen RC, Lindquist K, Kramer J, Miller B (2006) Subtype of mild cognitive impairment and progression to dementia and death. Dement Geriatr Cogn Disord 22:312–319
Yokota T, Mishra M, Akatsu H, Tani Y, Miyauchi T, Yamamoto T, Kosaka K, Nagai Y, Sawada T, Heese K (2006) Brain site-specific gene expression analysis in Alzheimer’s disease patients. Eur J Clin Investig 36:820–830
Zarow C, Lyness SA, Mortimer JA, Chui HC (2003) Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol 60:337–341