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INTRODUCTION: There is increasing interest in plasma A{beta} as an endophenotype and biomarker of Alzheimer's disease (AD). Identifying the genetic determinants of plasma A{beta} levels may elucidate important processes that determine plasma A{beta} measures. METHODS: We included 12,369 non-demented participants derived from eight population-based studies. Imputed genetic data and plasma A{beta}1-40, A{beta}1-42 levels and A{beta}1-42/A{beta}1-40 ratio were used to perform genome-wide association studies, gene-based and pathway analyses. Significant variants and genes were followed-up for the association with PET A{beta} deposition and AD risk. RESULTS: Single-variant analysis identified associations across APOE for A{beta}1-42 and A{beta}1-42/A{beta}1-40 ratio, and BACE1 for A{beta}1-40. Gene-based analysis of A{beta}1-40 additionally identified associations for APP, PSEN2, CCK and ZNF397. There was suggestive interaction between a BACE1 variant and APOE{varepsilon}4 on brain A{beta} deposition. DISCUSSION: Identification of variants near/in known major A{beta}-processing genes strengthens the relevance of plasma-A{beta} levels both as an endophenotype and a biomarker of AD.

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