Effects of Angiotensin-I-Converting Enzyme (ACE) Mutations Associated with Alzheimer's Disease on Blood ACE Phenotype.

ABSTRACT:

Backgrounds

Our recent analysis of 1200+ existing missense ACE mutations revealed that 400+ mutations are damaging and led us to hypothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer's disease (AD).

Methods

Here, we quantified blood ACE levels in EDTA plasma from 41 subjects with 10 different heterozygous ACE mutations, as well as 33 controls, and estimated the effect of these mutations on ACE phenotype using a set of mAbs to ACE and two ACE substrates.

Results

We found that relatively frequent (~1%) AD-associated ACE mutations in the N domain of ACE, Y215C, and G325R are truly damaging and likely transport-deficient, with the ACE levels in plasma at

SUBMITTER: Kryukova OV 

PROVIDER: S-EPMC11504702 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature