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Gepubliceerd in: Neuropraxis 2/2019

11-03-2019 | Artikel

Biomarkers voor de ziekte van Alzheimer: relaties met vasculaire factoren, neurodegeneratie en cognitie in de predementiële fasen

Auteurs: Isabelle Bos, Stephanie J. B. Vos, Frans R. J. Verhey, Pieter Jelle Visser

Gepubliceerd in: Neuropraxis | Uitgave 2/2019

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Samenvatting

Hoewel biomarkers het inzicht in de ziekte van Alzheimer (AD) hebben vergroot, bestaat er nog veel onduidelijkheid en is er nog geen effectieve behandeling beschikbaar voor deze complexe aandoening. Vanuit de literatuur zijn er aanwijzingen dat vasculaire aandoeningen en neurodegeneratieve processen geassocieerd zijn met dementie, maar het is tot dusver nog niet duidelijk hoe deze processen het ontstaan en beloop van AD beïnvloeden. In verschillende studies hebben wij de associaties tussen vasculaire en neurodegeneratieve processen en AD-biomarkers op grote schaal onderzocht, door bestaande data afkomstig uit verschillende bestaande bronnen opnieuw te gebruiken en te combineren. Uit de resultaten bleek dat vasculaire risicofactoren, met name hypertensie, bijdragen aan neurodegeneratieve schade in het brein en zo mogelijk cognitieve achteruitgang versnellen. Verder vonden we dat neurodegeneratieve processen, zoals synaptische disfunctie, axonale schade en astrogliale activiteit al geassocieerd zijn met AD voordat er sprake is van klinische symptomen. Daarnaast bleek dat vooral de hoeveelheid axonale schade geassocieerd is met cognitieve achteruitgang. Deze inzichten laten zien dat AD een multifactoriële ziekte is die een vroege, multifactoriële behandeling behoeft.
Literatuur
1.
go back to reference Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord. 1999;13(Suppl 3):S115–S23. CrossRefPubMed Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord. 1999;13(Suppl 3):S115–S23. CrossRefPubMed
2.
go back to reference Lo RY, Jagust WJ, Alzheimer’s Disease Neuroimaging I. Vascular burden and Alzheimer disease pathologic progression. Neurology. 2012;79(13):1349–55. CrossRefPubMedPubMedCentral Lo RY, Jagust WJ, Alzheimer’s Disease Neuroimaging I. Vascular burden and Alzheimer disease pathologic progression. Neurology. 2012;79(13):1349–55. CrossRefPubMedPubMedCentral
3.
go back to reference Vemuri P, Knopman DS. The role of cerebrovascular disease when there is concomitant Alzheimer disease. Biochim Biophys Acta. 2016;1862(5):952–6. CrossRefPubMed Vemuri P, Knopman DS. The role of cerebrovascular disease when there is concomitant Alzheimer disease. Biochim Biophys Acta. 2016;1862(5):952–6. CrossRefPubMed
4.
5.
go back to reference Raff MC, Whitmore AV, Finn JT. Axonal self-destruction and neurodegeneration. Science. 2002;296(5569):868–71. CrossRefPubMed Raff MC, Whitmore AV, Finn JT. Axonal self-destruction and neurodegeneration. Science. 2002;296(5569):868–71. CrossRefPubMed
6.
go back to reference Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405. CrossRefPubMedPubMedCentral Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405. CrossRefPubMedPubMedCentral
7.
go back to reference Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, et al. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292–323. CrossRefPubMedPubMedCentral Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, et al. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292–323. CrossRefPubMedPubMedCentral
8.
go back to reference Bos I. Biomarkers of Alzheimer’s disease: relations with vascular factors and cognition in the pre-dementia stages. Maastricht: Maastricht University; 2018. CrossRef Bos I. Biomarkers of Alzheimer’s disease: relations with vascular factors and cognition in the pre-dementia stages. Maastricht: Maastricht University; 2018. CrossRef
9.
go back to reference Breteler MM. Vascular risk factors for Alzheimer’s disease: an epidemiologic perspective. Neurobiol Aging. 2000;21(2):153–60. CrossRefPubMed Breteler MM. Vascular risk factors for Alzheimer’s disease: an epidemiologic perspective. Neurobiol Aging. 2000;21(2):153–60. CrossRefPubMed
11.
go back to reference Deckers K, Boxtel MP van, Schiepers OJ, Vugt M de, Munoz Sanchez JL, Anstey KJ, et al. Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int J Geriatr Psychiatry. 2015;30(3):234–46. CrossRefPubMed Deckers K, Boxtel MP van, Schiepers OJ, Vugt M de, Munoz Sanchez JL, Anstey KJ, et al. Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int J Geriatr Psychiatry. 2015;30(3):234–46. CrossRefPubMed
12.
go back to reference Bos I, Vos SJ, Frölich L, Kornhuber J, Wiltfang J, Maier W, et al. The frequency and influence of dementia risk factors in prodromal Alzheimer’s disease. Neurobiol Aging. 2017;56:33–40. CrossRefPubMed Bos I, Vos SJ, Frölich L, Kornhuber J, Wiltfang J, Maier W, et al. The frequency and influence of dementia risk factors in prodromal Alzheimer’s disease. Neurobiol Aging. 2017;56:33–40. CrossRefPubMed
13.
go back to reference D’Agostino RB Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743–53. CrossRefPubMed D’Agostino RB Sr., Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743–53. CrossRefPubMed
14.
go back to reference Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98. CrossRefPubMed Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98. CrossRefPubMed
15.
go back to reference Bos I, Verhey FR, Ramakers I, Jacobs HIL, Soininen H, Freund-Levi Y, et al. Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline. Alzheimers Res Ther. 2017;9(1):101. CrossRefPubMedPubMedCentral Bos I, Verhey FR, Ramakers I, Jacobs HIL, Soininen H, Freund-Levi Y, et al. Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline. Alzheimers Res Ther. 2017;9(1):101. CrossRefPubMedPubMedCentral
16.
go back to reference Zetterberg H, Skillback T, Mattsson N, Trojanowski JQ, Portelius E, Shaw LM, et al. Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol. 2016;73(1):60–7. CrossRefPubMedPubMedCentral Zetterberg H, Skillback T, Mattsson N, Trojanowski JQ, Portelius E, Shaw LM, et al. Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol. 2016;73(1):60–7. CrossRefPubMedPubMedCentral
17.
go back to reference Bruno D, Pomara N, Nierenberg J, Ritchie JC, Lutz MW, Zetterberg H, et al. Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants. Exp Gerontol. 2012;47(5):347–52. CrossRefPubMed Bruno D, Pomara N, Nierenberg J, Ritchie JC, Lutz MW, Zetterberg H, et al. Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants. Exp Gerontol. 2012;47(5):347–52. CrossRefPubMed
18.
go back to reference Antonell A, Mansilla A, Rami L, Llado A, Iranzo A, Olives J, et al. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis. 2014;42(3):901–8. CrossRefPubMed Antonell A, Mansilla A, Rami L, Llado A, Iranzo A, Olives J, et al. Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis. 2014;42(3):901–8. CrossRefPubMed
19.
go back to reference Portelius E, Zetterberg H, Skillback T, Tornqvist U, Andreasson U, Trojanowski JQ, et al. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain. 2015;138(Pt 11):3373–85. CrossRefPubMedPubMedCentral Portelius E, Zetterberg H, Skillback T, Tornqvist U, Andreasson U, Trojanowski JQ, et al. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain. 2015;138(Pt 11):3373–85. CrossRefPubMedPubMedCentral
20.
go back to reference Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P, et al. Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer Disease. JAMA Neurol. 2015;72(11):1275–80. CrossRefPubMedPubMedCentral Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P, et al. Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer Disease. JAMA Neurol. 2015;72(11):1275–80. CrossRefPubMedPubMedCentral
21.
go back to reference Bos I, Vos SJB, Vandenberghe R, Scheltens P, Engelborghs S, Frisoni G, et al. The EMIF-AD multimodal biomarker discovery study: design, methods and cohort characteristics. Alzheimers Res Ther. 2018;10(1):64. CrossRefPubMedPubMedCentral Bos I, Vos SJB, Vandenberghe R, Scheltens P, Engelborghs S, Frisoni G, et al. The EMIF-AD multimodal biomarker discovery study: design, methods and cohort characteristics. Alzheimers Res Ther. 2018;10(1):64. CrossRefPubMedPubMedCentral
22.
go back to reference Degerman Gunnarsson M, Ingelsson M, Blennow K, Basun H, Lannfelt L, Kilander L. High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease. Alzheimers Res Ther. 2016;8(1):22. CrossRefPubMedPubMedCentral Degerman Gunnarsson M, Ingelsson M, Blennow K, Basun H, Lannfelt L, Kilander L. High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease. Alzheimers Res Ther. 2016;8(1):22. CrossRefPubMedPubMedCentral
23.
go back to reference Brier MR, Gordon B, Friedrichsen K, McCarthy J, Stern A, Christensen J, et al. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med. 2016;8(338):338ra66.. CrossRefPubMedPubMedCentral Brier MR, Gordon B, Friedrichsen K, McCarthy J, Stern A, Christensen J, et al. Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease. Sci Transl Med. 2016;8(338):338ra66.. CrossRefPubMedPubMedCentral
24.
go back to reference Mormino EC, Betensky RA, Hedden T, Schultz AP, Amariglio RE, Rentz DM, et al. Synergistic effect of beta-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 2014;71(11):1379–85. CrossRefPubMedPubMedCentral Mormino EC, Betensky RA, Hedden T, Schultz AP, Amariglio RE, Rentz DM, et al. Synergistic effect of beta-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 2014;71(11):1379–85. CrossRefPubMedPubMedCentral
25.
go back to reference Jack CR Jr., Knopman DS, Chetelat G, Dickson D, Fagan AM, Frisoni GB, et al. Suspected non-Alzheimer disease pathophysiology—concept and controversy. Nat Rev Neurol. 2016;12(2):117–24. CrossRefPubMedPubMedCentral Jack CR Jr., Knopman DS, Chetelat G, Dickson D, Fagan AM, Frisoni GB, et al. Suspected non-Alzheimer disease pathophysiology—concept and controversy. Nat Rev Neurol. 2016;12(2):117–24. CrossRefPubMedPubMedCentral
26.
go back to reference Mattsson N, Insel PS, Palmqvist S, Portelius E, Zetterberg H, Weiner M, et al. Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer’s disease. EMBO Mol Med. 2016;8(10):1184–96. CrossRefPubMedPubMedCentral Mattsson N, Insel PS, Palmqvist S, Portelius E, Zetterberg H, Weiner M, et al. Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer’s disease. EMBO Mol Med. 2016;8(10):1184–96. CrossRefPubMedPubMedCentral
27.
go back to reference Braak H, Zetterberg H, Del Tredici K, Blennow K. Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-beta changes occur before increases of tau in cerebrospinal fluid. Acta Neuropathol. 2013;126(5):631–41. CrossRefPubMed Braak H, Zetterberg H, Del Tredici K, Blennow K. Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-beta changes occur before increases of tau in cerebrospinal fluid. Acta Neuropathol. 2013;126(5):631–41. CrossRefPubMed
28.
go back to reference Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184–5. CrossRefPubMed Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992;256(5054):184–5. CrossRefPubMed
29.
go back to reference Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Lowe VJ, Graff-Radford J, et al. Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann Neurol. 2017;82(5):706–18. CrossRefPubMedPubMedCentral Vemuri P, Lesnick TG, Przybelski SA, Knopman DS, Lowe VJ, Graff-Radford J, et al. Age, vascular health, and Alzheimer disease biomarkers in an elderly sample. Ann Neurol. 2017;82(5):706–18. CrossRefPubMedPubMedCentral
30.
go back to reference Vemuri P, Knopman DS, Lesnick TG, Przybelski SA, Mielke MM, Graff-Radford J, et al. Evaluation of amyloid protective factors and alzheimer disease neurodegeneration protective factors in elderly individuals. Jama Neurol. 2017;74(6):718–26. CrossRefPubMedPubMedCentral Vemuri P, Knopman DS, Lesnick TG, Przybelski SA, Mielke MM, Graff-Radford J, et al. Evaluation of amyloid protective factors and alzheimer disease neurodegeneration protective factors in elderly individuals. Jama Neurol. 2017;74(6):718–26. CrossRefPubMedPubMedCentral
31.
go back to reference Hesse C, Rosengren L, Andreasen N, Davidsson P, Vanderstichele H, Vanmechelen E, et al. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett. 2001;297(3):187–90. CrossRefPubMed Hesse C, Rosengren L, Andreasen N, Davidsson P, Vanderstichele H, Vanmechelen E, et al. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett. 2001;297(3):187–90. CrossRefPubMed
32.
go back to reference Mullard A. Sting of Alzheimer’s failures offset by upcoming prevention trials. Nat Rev Drug Discov. 2012;11(9):657–60. CrossRefPubMed Mullard A. Sting of Alzheimer’s failures offset by upcoming prevention trials. Nat Rev Drug Discov. 2012;11(9):657–60. CrossRefPubMed
33.
go back to reference Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med. 2014;6(228):228fs13. CrossRefPubMedPubMedCentral Sperling RA, Rentz DM, Johnson KA, Karlawish J, Donohue M, Salmon DP, et al. The A4 study: stopping AD before symptoms begin? Sci Transl Med. 2014;6(228):228fs13. CrossRefPubMedPubMedCentral
34.
go back to reference Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Trends Mol Med. 2015;21(6):394–402. CrossRefPubMed Pedersen JT, Sigurdsson EM. Tau immunotherapy for Alzheimer’s disease. Trends Mol Med. 2015;21(6):394–402. CrossRefPubMed
36.
go back to reference Nistico R, Pignatelli M, Piccinin S, Mercuri NB, Collingridge G. Targeting synaptic dysfunction in Alzheimer’s disease therapy. Mol Neurobiol. 2012;46(3):572–87. CrossRefPubMed Nistico R, Pignatelli M, Piccinin S, Mercuri NB, Collingridge G. Targeting synaptic dysfunction in Alzheimer’s disease therapy. Mol Neurobiol. 2012;46(3):572–87. CrossRefPubMed
37.
go back to reference Shadfar S, Hwang CJ, Lim MS, Choi DY, Hong JT. Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents. Arch Pharm Res. 2015;38(12):2106–19. CrossRefPubMed Shadfar S, Hwang CJ, Lim MS, Choi DY, Hong JT. Involvement of inflammation in Alzheimer’s disease pathogenesis and therapeutic potential of anti-inflammatory agents. Arch Pharm Res. 2015;38(12):2106–19. CrossRefPubMed
38.
go back to reference Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–734. CrossRefPubMed Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet. 2017;390(10113):2673–734. CrossRefPubMed
Metagegevens
Titel
Biomarkers voor de ziekte van Alzheimer: relaties met vasculaire factoren, neurodegeneratie en cognitie in de predementiële fasen
Auteurs
Isabelle Bos
Stephanie J. B. Vos
Frans R. J. Verhey
Pieter Jelle Visser
Publicatiedatum
11-03-2019
Uitgeverij
Bohn Stafleu van Loghum
Gepubliceerd in
Neuropraxis / Uitgave 2/2019
Print ISSN: 1387-5817
Elektronisch ISSN: 1876-5785
DOI
https://doi.org/10.1007/s12474-019-00215-5