Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.

TitlePlasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.
Publication TypeJournal Article
Year of Publication2021
AuthorsDamotte, V, van der Lee, SJ, Chouraki, V, Grenier-Boley, B, Simino, J, Adams, H, Tosto, G, White, C, Terzikhan, N, Cruchaga, C, Knol, MJ, Li, S, Schraen, S, Grove, ML, Satizabal, C, Amin, N, Berr, C, Younkin, S, Gottesman, RF, Buée, L, Beiser, A, Knopman, DS, Uitterlinden, A, DeCarli, C, Bressler, J, DeStefano, A, Dartigues, J-F, Yang, Q, Boerwinkle, E, Tzourio, C, Fornage, M, M Ikram, A, Amouyel, P, de Jager, P, Reitz, C, Mosley, TH, Lambert, J-C, Seshadri, S, van Duijn, CM
Corporate AuthorsAlzheimer's Disease Neuroimaging Initiative
JournalAlzheimers Dement
Date Published2021 May 18
ISSN1552-5279
Abstract

INTRODUCTION: There 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.

METHODS: We 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.

RESULTS: Single-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.

DISCUSSION: Identification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD.

DOI10.1002/alz.12333
Alternate JournalAlzheimers Dement
PubMed ID34002480