作者
Vincent Damotte, Sven J van der Lee, Vincent Chouraki, Benjamin Grenier‐Boley, Jeannette Simino, Hieab Adams, Giuseppe Tosto, Charles White, Natalie Terzikhan, Carlos Cruchaga, Maria J Knol, Shuo Li, Susanna Schraen, Megan L Grove, Claudia Satizabal, Najaf Amin, Claudine Berr, Steven Younkin, Alzheimer's Disease Neuroimaging Initiative, Rebecca F Gottesman, Luc Buée, Alexa Beiser, David S Knopman, Andre Uitterlinden, Charles DeCarli, Jan Bressler, Anita DeStefano, Jean‐François Dartigues, Qiong Yang, Eric Boerwinkle, Christophe Tzourio, Myriam Fornage, M Arfan Ikram, Philippe Amouyel, Phil de Jager, Christiane Reitz, Thomas H Mosley, Jean‐Charles Lambert, Sudha Seshadri, Cornelia M van Duijn
发表日期
2021/5/18
期刊
Alzheimer's & Dementia
简介
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 …
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