Alzheimer's disease risk ABCA7 p.A696S variant disturbs the microglial response to amyloid pathology in mice.

ABSTRACT: The adenosine triphosphate-binding cassette transporter A7 (ABCA7) gene is ranked as one of the top susceptibility loci for Alzheimer's disease (AD). While ABCA7 mediates lipid transport across cellular membranes, ABCA7 loss of function has been shown to exacerbate amyloid-β (Aβ) pathology and compromise microglial function. Our family-based study uncovered an extremely rare ABCA7 p.A696S variant that was substantially segregated with the development of AD in 3 African American families. Using the knockin mouse model, we investigated the effects of ABCA7-A696S substitution on amyloid pathology and brain immune response in 5xFAD transgenic mice. Importantly, our study demonstrated that ABCA7-A696S substitution reduces amyloid plaque-associated microgliosis and increases dystrophic neurites

SUBMITTER: Ma X 

PROVIDER: S-EPMC11884743 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature