Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Các mối liên hệ của NfL, GFAP và t-tau trong huyết tương với bệnh mạch máu nhỏ não và bệnh mất trí nhớ khởi phát: Dữ liệu theo chiều dọc từ Nghiên cứu AGES-Reykjavik
GeroScience - Trang 1-12 - 2023
Tóm tắt
Chúng tôi đã điều tra mối liên hệ của neurofilament nhẹ (NfL) trong huyết tương, protein axit fibrillarin tủy (GFAP) và total tau (t-tau) với các chỉ số của bệnh mạch máu nhỏ não (SVD) và với bệnh mất trí nhớ khởi phát. Chúng tôi cũng đã xem xét liệu các mối liên hệ của NfL, GFAP và t-tau với bệnh mất trí nhớ khởi phát có được giải thích bởi SVD hay không. Dữ liệu được lấy từ một mẫu phụ ngẫu nhiên (n = 1069) trong Nghiên cứu AGES-Reykjavik dân số, những người đã trải qua chụp MRI não và trong đó NfL, GFAP và t-tau trong huyết tương đã được đo tại thời điểm bắt đầu (76.1 ± 5.4 tuổi/55.9% là nữ/điểm bắt đầu 2002–2006/theo dõi cho đến năm 2015). Một điểm số gánh nặng SVD tổng hợp đã được tính toán dựa trên thể tích tăng cường chất trắng (WMHV), nhồi máu dưới vỏ, chảy máu vi mạch não và không gian lớn quanh mạch. Bệnh mất trí nhớ được đánh giá theo quy trình 3 bước và được xét duyệt bởi các chuyên gia. NfL cao hơn liên quan đến điểm số gánh nặng SVD cao hơn. Bệnh mất trí nhớ đã xảy ra ở 225 (21.0%) cá nhân. Điểm số gánh nặng SVD giải thích một phần quan trọng của mối liên hệ giữa NfL và bệnh mất trí nhớ khởi phát. WMHV đóng góp mạnh mẽ nhất vào hiệu ứng đã được giải thích. GFAP không liên quan đến điểm số gánh nặng SVD, nhưng có liên quan đến WMHV, và WMHV đã giải thích một phần quan trọng của mối liên hệ giữa GFAP và bệnh mất trí nhớ khởi phát. T-tau có liên quan đến WMHV, nhưng không có liên quan đến bệnh mất trí nhớ khởi phát. Tóm lại, dấu hiệu liên quan mạnh mẽ nhất đến SVD là NfL trong huyết tương, mà mối liên hệ với WMHV dường như giải thích một phần của mối liên hệ này với bệnh mất trí nhớ khởi phát. Nghiên cứu này gợi ý rằng NfL trong huyết tương có thể phản ánh sự đóng góp của bệnh mạch máu đi kèm đối với bệnh mất trí nhớ. Tuy nhiên, độ lớn của hiệu ứng được giải thích là tương đối nhỏ, và cần thêm nghiên cứu để điều tra những hệ lụy lâm sàng của phát hiện này.
Từ khóa
#neurofilament nhẹ #GFAP #t-tau #bệnh mạch máu nhỏ não #bệnh mất trí nhớ khởi phát #nghiên cứu AGES-ReykjavikTài liệu tham khảo
Teunissen CE, Verberk IMW, Thijssen EH, Vermunt L, Hansson O, Zetterberg H, van der Flier WM, Mielke MM, Del Campo M. Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol. 2022;21:66–77. https://doi.org/10.1016/S1474-4422(21)00361-6.
Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, Barro C, Kappos L, Comabella M, Fazekas F, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14:577–89. https://doi.org/10.1038/s41582-018-0058-z.
Gaetani L, Blennow K, Calabresi P, Di Filippo M, Parnetti L, Zetterberg H. Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatry. 2019;90:870–81. https://doi.org/10.1136/jnnp-2018-320106.
Middeldorp J, Hol EM. GFAP in health and disease. Prog Neurobiol. 2011;93:421–43. https://doi.org/10.1016/j.pneurobio.2011.01.005.
Yang Z, Wang KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015;38:364–74. https://doi.org/10.1016/j.tins.2015.04.003.
Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–62. https://doi.org/10.1016/j.jalz.2018.02.018.
van Sloten TT, Sedaghat S, Carnethon MR, Launer LJ, Stehouwer CDA. Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Lancet Diabetes Endocrinol. 2020;8:325–36. https://doi.org/10.1016/S2213-8587(19)30405-X.
Wardlaw JM, Smith C, Dichgans M. Small vessel disease: mechanisms and clinical implications. Lancet Neurol. 2019;18:684–96. https://doi.org/10.1016/S1474-4422(19)30079-1.
Rajan KB, Aggarwal NT, McAninch EA, Weuve J, Barnes LL, Wilson RS, DeCarli C, Evans DA. Remote blood biomarkers of longitudinal cognitive outcomes in a population study. Ann Neurol. 2020;88:1065–76. https://doi.org/10.1002/ana.25874.
de Wolf F, Ghanbari M, Licher S, McRae-McKee K, Gras L, Weverling GJ, Wermeling P, Sedaghat S, Ikram MK, Waziry R, et al. Plasma tau, neurofilament light chain and amyloid-beta levels and risk of dementia; a population-based cohort study. Brain. 2020;143:1220–32. https://doi.org/10.1093/brain/awaa054.
Gonzales MM, Wiedner C, Wang CP, Liu Q, Bis JC, Li Z, Himali JJ, Ghosh S, Thomas EA, Parent DM, et al. A population-based meta-analysis of circulating GFAP for cognition and dementia risk. Ann Clin Transl Neurol. 2022;9:1574–85. https://doi.org/10.1002/acn3.51652.
Pase MP, Beiser AS, Himali JJ, Satizabal CL, Aparicio HJ, DeCarli C, Chene G, Dufouil C, Seshadri S. Assessment of plasma total tau level as a predictive biomarker for dementia and related endophenotypes. JAMA Neurol. 2019;76:598–606. https://doi.org/10.1001/jamaneurol.2018.4666.
Marks JD, Syrjanen JA, Graff-Radford J, Petersen RC, Machulda MM, Campbell MR, Algeciras-Schimnich A, Lowe V, Knopman DS, Jack CR Jr, et al. Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes. Alzheimers Res Ther. 2021;13:199. https://doi.org/10.1186/s13195-021-00944-y.
McCarter SJ, Lesnick TG, Lowe VJ, Rabinstein AA, Przybelski SA, Algeciras-Schimnich A, Ramanan VK, Jack CR, Petersen RC, Knopman DS, et al. Association between plasma biomarkers of amyloid, tau, and neurodegeneration with cerebral microbleeds. J Alzheimers Dis. 2022;87:1537–47. https://doi.org/10.3233/JAD-220158.
Dittrich A, Ashton NJ, Zetterberg H, Blennow K, Simren J, Geiger F, Zettergren A, Shams S, Machado A, Westman E, et al. Plasma and CSF NfL are differentially associated with biomarker evidence of neurodegeneration in a community-based sample of 70-year-olds. Alzheimers Dement (Amst). 2022;14:e12295. https://doi.org/10.1002/dad2.12295.
Fohner AE, Bartz TM, Tracy RP, Adams HHH, Bis JC, Djousse L, Satizabal CL, Lopez OL, Seshadri S, Mukamal KJ, et al. Association of serum neurofilament light chain concentration and MRI findings in older adults: the cardiovascular health study. Neurology. 2022;98:e903–11. https://doi.org/10.1212/WNL.0000000000013229.
Shir D, Graff-Radford J, Hofrenning EI, Lesnick TG, Przybelski SA, Lowe VJ, Knopman DS, Petersen RC, Jack CR Jr, Vemuri P, et al. Association of plasma glial fibrillary acidic protein (GFAP) with neuroimaging of Alzheimer’s disease and vascular pathology. Alzheimers Dement (Amst). 2022;14:e12291. https://doi.org/10.1002/dad2.12291.
Romero JR, Demissie S, Beiser A, Himali JJ, DeCarli C, Levy D, Seshadri S. Relation of plasma beta-amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study. Ann Clin Transl Neurol. 2020;7:1083–91. https://doi.org/10.1002/acn3.51066.
Zlokovic BV, Gottesman RF, Bernstein KE, Seshadri S, McKee A, Snyder H, Greenberg SM, Yaffe K, Schaffer CB, Yuan C, et al. Vascular contributions to cognitive impairment and dementia (VCID): a report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop. Alzheimers Dement. 2020;16:1714–33. https://doi.org/10.1002/alz.12157.
Rensma SP, van Sloten TT, Launer LJ, Stehouwer CDA. Cerebral small vessel disease and risk of incident stroke, dementia and depression, and all-cause mortality: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2018;90:164–73. https://doi.org/10.1016/j.neubiorev.2018.04.003.
Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G, Thorgeirsson G, Aspelund T, Garcia ME, Cotch MF, et al. Age, Gene/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics. Am J Epidemiol. 2007;165:1076–87. https://doi.org/10.1093/aje/kwk115.
Wilcock D, Jicha G, Blacker D, Albert MS, D’Orazio LM, Elahi FM, Fornage M, Hinman JD, Knoefel J, Kramer J, et al. MarkVCID cerebral small vessel consortium: I. Enrollment, clinical, fluid protocols. Alzheimers Dement. 2021;17:704–15. https://doi.org/10.1002/alz.12215.
O’Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S, Bazenet C, Soares H, Lovestone S, Hampel H, et al. Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research. Alzheimers Dement. 2015;11:549–60. https://doi.org/10.1016/j.jalz.2014.08.099.
Sveinbjornsdottir S, Sigurdsson S, Aspelund T, Kjartansson O, Eiriksdottir G, Valtysdottir B, Lopez OL, van Buchem MA, Jonsson PV, Gudnason V, et al. Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location. J Neurol Neurosurg Psychiatry. 2008;79:1002–6. https://doi.org/10.1136/jnnp.2007.121913.
Scher AI, Gudmundsson LS, Sigurdsson S, Ghambaryan A, Aspelund T, Eiriksdottir G, van Buchem MA, Gudnason V, Launer LJ. Migraine headache in middle age and late-life brain infarcts. JAMA. 2009;301:2563–70. https://doi.org/10.1001/jama.2009.932.
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O’Brien JT, Barkhof F, Benavente OR, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822–38. https://doi.org/10.1016/S1474-4422(13)70124-8.
Sigurdsson S, Aspelund T, Forsberg L, Fredriksson J, Kjartansson O, Oskarsdottir B, Jonsson PV, Eiriksdottir G, Harris TB, Zijdenbos A, et al. Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study. Neuroimage. 2012;59:3862–70. https://doi.org/10.1016/j.neuroimage.2011.11.024.
Ding J, Sigurethsson S, Jonsson PV, Eiriksdottir G, Charidimou A, Lopez OL, van Buchem MA, Guethnason V, Launer LJ. Large perivascular spaces visible on magnetic resonance imaging, cerebral small vessel disease progression, and risk of dementia: the Age. Gene/Environment Susceptibility-Reykjavik Study JAMA Neurol. 2017;74:1105–12. https://doi.org/10.1001/jamaneurol.2017.1397.
Sigurdsson S, Aspelund T, Kjartansson O, Gudmundsson E, Jonsson PV, van Buchem MA, Gudnason V, Launer LJ. Cerebrovascular risk-factors of prevalent and incident brain infarcts in the general population: the AGES-Reykjavik Study. Stroke. 2022;53:1199–206. https://doi.org/10.1161/STROKEAHA.121.034130.
Ding J, Sigurdsson S, Garcia M, Phillips CL, Eiriksdottir G, Gudnason V, van Buchem MA, Launer LJ. Risk factors associated with incident cerebral microbleeds according to location in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. JAMA Neurol. 2015;72:682–8. https://doi.org/10.1001/jamaneurol.2015.0174.
Vonk JMJ, Greving JP, Gudnason V, Launer LJ, Geerlings MI. Dementia risk in the general population: large-scale external validation of prediction models in the AGES-Reykjavik study. Eur J Epidemiol. 2021;36:1025–41. https://doi.org/10.1007/s10654-021-00785-x.
Saczynski JS, Sigurdsson S, Jonsdottir MK, Eiriksdottir G, Jonsson PV, Garcia ME, Kjartansson O, Lopez O, van Buchem MA, Gudnason V, et al. Cerebral infarcts and cognitive performance: importance of location and number of infarcts. Stroke. 2009;40:677–82. https://doi.org/10.1161/STROKEAHA.108.530212.
Morris JN, Hawes C, Fries BE, Phillips CD, Mor V, Katz S, Murphy K, Drugovich ML, Friedlob AS. Designing the national resident assessment instrument for nursing homes. Gerontologist. 1990;30:293–307. https://doi.org/10.1093/geront/30.3.293.
Rensma SP, van Sloten TT, Ding J, Sigurdsson S, Stehouwer CDA, Gudnason V, Launer LJ. Type 2 diabetes, change in depressive symptoms over time, and cerebral small vessel disease: longitudinal data of the AGES-Reykjavik Study. Diabetes Care. 2020;43:1781–7. https://doi.org/10.2337/dc19-2437.
Zhou TL, Rensma SP, van der Heide FCT, Henry RMA, Kroon AA, Houben A, Jansen JFA, Backes WH, Berendschot T, Schouten J, et al. Blood pressure variability and microvascular dysfunction: the Maastricht Study. J Hypertens. 2020;38:1541–50. https://doi.org/10.1097/HJH.0000000000002444.
Rijnhart JJM, Twisk JWR, Eekhout I, Heymans MW. Comparison of logistic-regression based methods for simple mediation analysis with a dichotomous outcome variable. BMC Med Res Methodol. 2019;19:19. https://doi.org/10.1186/s12874-018-0654-z.
Hakim AM. Small vessel disease. Front Neurol. 2019;10:1020. https://doi.org/10.3389/fneur.2019.01020.
Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, Brayne C, Burns A, Cohen-Mansfield J, Cooper C, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396:413–46. https://doi.org/10.1016/S0140-6736(20)30367-6.
Barro C, Chitnis T, Weiner HL. Blood neurofilament light: a critical review of its application to neurologic disease. Ann Clin Transl Neurol. 2020;7:2508–23. https://doi.org/10.1002/acn3.51234.
Song R, Xu H, Dintica CS, Pan KY, Qi X, Buchman AS, Bennett DA, Xu W. Associations between cardiovascular risk, structural brain changes, and cognitive decline. J Am Coll Cardiol. 2020;75:2525–34. https://doi.org/10.1016/j.jacc.2020.03.053.
Lamar M, Boots EA, Arfanakis K, Barnes LL, Schneider JA. Common brain structural alterations associated with cardiovascular disease risk factors and Alzheimer’s dementia: future directions and implications. Neuropsychol Rev. 2020;30:546–57. https://doi.org/10.1007/s11065-020-09460-6.
Stocker H, Beyer L, Perna L, Rujescu D, Holleczek B, Beyreuther K, Stockmann J, Schottker B, Gerwert K, Brenner H. Association of plasma biomarkers, p-tau181, glial fibrillary acidic protein, and neurofilament light, with intermediate and long-term clinical Alzheimer’s disease risk: Results from a prospective cohort followed over 17 years. Alzheimers Dement. 2022. https://doi.org/10.1002/alz.12614.
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer’s disease. Lancet. 2021;397:1577–90. https://doi.org/10.1016/S0140-6736(20)32205-4.
Heshmatollah A, Fani L, Koudstaal PJ, Ghanbari M, Ikram MA, Ikram MK. Plasma beta-amyloid, total-tau, and neurofilament light hain levels and the risk of stroke: a prospective population-based study. Neurology. 2022;98:e1729–37. https://doi.org/10.1212/WNL.0000000000200004.
Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladacenco O, Roza E, Costachescu B, Grumezescu AM, Teleanu RI. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases. Int J Mol Sci. 2022;23(11):593. https://doi.org/10.3390/ijms23115938.
Mattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E, Palmqvist S, Baker D, Tan Hehir CA, Jeromin A, et al. Plasma tau in Alzheimer disease. Neurology. 2016;87:1827–35. https://doi.org/10.1212/WNL.0000000000003246.
Planche V, Bouteloup V, Pellegrin I, Mangin JF, Dubois B, Ousset PJ, Pasquier F, Blanc F, Paquet C, Hanon O, et al. Validity and performance of blood biomarkers for Alzheimer disease to predict dementia risk in a large clinic-based cohort. Neurology. 2022. https://doi.org/10.1212/WNL.0000000000201479.