The Abca7^V1613M variant reduces Aβ generation, plaque load, and neuronal damage.

ABSTRACT:

Background

Variants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD).

Methods

CRISPR-Cas9 was used to generate an Abca7^V1613M variant in mice, modeling the homologous human ABCA7^V1599M variant, and extensive characterization was performed.

Results

Abca7^V1613M microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity. Homozygous Abca7^V1613M mice display elevated circulating cholesterol and altered brain lipid composition. When crossed with 5xFAD mice, homozygous Abca7^V1613M mice display fewer Thioflavin S-positive plaques, decreased amyloid beta (Aβ) pept

SUBMITTER: Butler CA 

PROVIDER: S-EPMC11247689 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature