Reduced secreted clusterin as a mechanism for Alzheimer-associated CLU mutations.

ABSTRACT:

Background

The clusterin (CLU) gene has been identified as an important risk locus for Alzheimer's disease (AD). Although the actual risk-increasing polymorphisms at this locus remain to be identified, we previously observed an increased frequency of rare non-synonymous mutations and small insertion-deletions of CLU in AD patients, which specifically clustered in the β-chain domain of CLU. Nonetheless the pathogenic nature of these variants remained unclear. Here we report a novel non-synonymous CLU mutation (p.I360N) in a Belgian Alzheimer patient and have explored the pathogenic nature of this and 10 additional CLU mutations on protein localization and secretion in vitro using immunocytochemistry, immunodetection and ELISAs.

Results

Three patient-specific CLU mutations in

SUBMITTER: Bettens K 

PROVIDER: S-EPMC4502563 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature