Ms4a4a deficiency ameliorates plaque pathology in a mouse model of amyloid accumulation.

ABSTRACT:

Introduction

Genome-wide association studies have identified MS4A4A, a microglia-enriched gene, as a modulator of Alzheimer's disease (AD) risk. Common variants in MS4A4A affect AD susceptibility, gene expression, triggering receptor expressed on myeloid cells 2 (TREM2) signaling, and microglial transcriptional states, but the gene's functional role remains unclear.

Methods

Using a novel model, we investigated the impact of Ms4a4a loss in the 5xFAD mouse model of amyloid beta (Aβ) accumulation.

Results

Ms4a4a deficiency reduced steady-state Aβ levels and shortened its half-life in brain interstitial fluid. Aged 5xFAD mice lacking Ms4a4a exhibited more compact plaques and lower overall plaque burden. Microglia deficient in Ms4a4a showed a pro-inflammatory profile and e

SUBMITTER: Danhash EP 

PROVIDER: S-EPMC12371455 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature