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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease

Lookup NU author(s): Dr Dag Aarsland, Professor David BrooksORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

INTRODUCTION: APOE ε4 is the major genetic risk factor for Alzheimer’s disease (AD), but its prevalence is unclear since earlier studies did not require biomarker evidence of amyloid-β (Aβ) pathology. METHODS: We included 3,451 Aβ + subjects (853 AD-type dementia, 1,810 mild cognitive impairment (MCI), and 788 cognitively normal (CN)). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education and geographical location. RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in MCI and 51% in CN, and decreased with advancing age in Aβ+ CN and Aβ+ MCI (p<0.05), but not in Aβ+ AD dementia (p=0.66). The prevalence was highest in Northern Europe, but did not vary by sex or education. DISCUSSION: The APOE ε4 prevalence in AD was higher than in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.


Publication metadata

Author(s): Mattsson N, Groot C, Jansen WJ, Landau SM, Villemagne VL, Engelborghs S, Mintun MM, Lleo A, Molinuevo JL, Jagust WJ, Frisoni GB, Ivanoiu A, Chételat G, Oliveira CRD, Rodrigue KM, Kornhuber J, Wallin A, Klimkowicz-Mrowiec A, Kandimalla R, Popp J, Aalten PP, Aarsland D, Alcolea D, Almdahl IS, Baldeiras I, van Buchem MA, Cavedo E, Chen K, Cohen AD, Förster S, Fortea J, Frederiksen KS, Freund-Levi Y, Gill KD, Gkatzima O, Grimmer T, Hampel H, Herukka SK, Johannsen P, van Laere K, de Leon MJ, Maier W, Marcusson J, Meulenbroek O, Møllergård HM, Morris JC, Mroczko B, Nordlund A, Prabhakar S, Peters O, Rami L, Rodríguez-Rodríguez E, Roe CM, Rüther E, Santana I, Schröder J, Seo SW, Soininen H, Spiru L, Stomrud E, Struyfs H, Teunissen CE, Verhey FRJ, Vos SJB, van Doorn LJCVW, Waldemar G, Wallin AK, Wiltfang J, Vandenberghe R, Brooks DJ, Fladby T, Rowe CC, Drzezga A, Verbeek MM, Sarazin M, Wolk DA, Fleisher AS, Klunk WE, Na DL, Sánchez-Juan P, Lee DY, Nordberg A, Tsolaki M, Camus V, Rinne JO, Fagan AM, Zetterberg H, Blennow K, Rabinovici GD, Hansson O, van Berckel BNM, van der Flier WM, Scheltens P, Visser PJ, Ossenkoppele R

Publication type: Article

Publication status: Published

Journal: Alzheimer's and Dementia

Year: 2018

Volume: 14

Issue: 7

Pages: 913-924

Print publication date: 01/07/2018

Online publication date: 28/03/2018

Acceptance date: 27/02/2018

Date deposited: 27/02/2018

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.jalz.2018.02.009

DOI: 10.1016/j.jalz.2018.02.009


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Funding

Funder referenceFunder name
P50AG005681
P01AG003991
P01AG026276
U19AG032438

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