Influence of Coding Variability in APP-A? Metabolism Genes in Sporadic Alzheimer's Disease.

ABSTRACT: The cerebral deposition of A?42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP), is a central event in Alzheimer's disease (AD)(Amyloid hypothesis). Given the key role of APP-A? metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, A? degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4

SUBMITTER: Sassi C 

PROVIDER: S-EPMC4889076 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature