Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience.

ABSTRACT:

Background

While age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline.

Methods

We used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths. Second, we used whole genome sequences to identify candidate SNPs in significant linkage regions. Third, we replicated SNPs from the linkage peaks that reduced risk for AD in an independent dataset and in a gene-based test. Finally, we experim

SUBMITTER: Ridge PG 

PROVIDER: S-EPMC5706401 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature