Carriers of Heterozygous Loss-of-Function ACE Mutations Are at Risk for Alzheimer's Disease.

ABSTRACT: We hypothesized that subjects with heterozygous loss-of-function (LoF) ACE mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the protein aggregates that accumulate in the brains of AD patients, is cleaved by ACE (angiotensin I-converting enzyme). Thus, decreased ACE activity in the brain, either due to genetic mutation or the effects of ACE inhibitors, could be a risk factor for AD. To explore this hypothesis in the current study, existing SNP databases were analyzed for LoF ACE mutations using four predicting tools, including PolyPhen-2, and compared with the topology of known ACE mutations already associated with AD. The combined frequency of >400 of these LoF-damaging ACE mutations in the general population is quite si

SUBMITTER: Danilov SM 

PROVIDER: S-EPMC10813023 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature