Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

IntroductionThere is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures.MethodsWe included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk.ResultsSingle-variant analysis identified associations with apolipoprotein E (APOE) for Aβ1-42 and Aβ1-42/Aβ1-40 ratio, and BACE1 for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition.DiscussionIdentification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD.

Original publication

DOI

10.1002/alz.12333

Type

Journal article

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association

Publication Date

10/2021

Volume

17

Pages

1663 - 1674

Addresses

Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.

Keywords

Alzheimer's Disease Neuroimaging Initiative, Brain, Humans, Alzheimer Disease, Amyloid, Amyloid beta-Protein Precursor, Apolipoproteins E, Positron-Emission Tomography, Amyloid Precursor Protein Secretases, Presenilin-2, Genome-Wide Association Study, Aspartic Acid Endopeptidases, Healthy Volunteers