Ms4a4a loss preferentially remodels microglia with limited, compartment-specific effects across central and peripheral immune compartments in 5xFAD mice

In 5xFAD mice, constitutive Ms4a4a loss most strongly remodels brain microglia, increasing abundance, CD86, MHC class II intensity, and CXCR4-high microglia.

• Why it matters: MS4A locus variants modify Alzheimer’s disease risk, but Ms4a4a’s microglial enrichment and peripheral myeloid expression leave unclear whether its effects extend beyond brain-resident cells.
• What they did: The study used multicompartment flow cytometry profiling in 5xFAD Ms4a4a wild-type versus Ms4a4a-deficient mice across brain, dural meninges, skull bone marrow, tibial bone marrow, and spleen.
• The result: Effects were limited and compartment-specific outside microglia: brain macrophages increased MHC class II, brain cDCs decreased MHC class II, dura/skull composition was largely preserved, and tibial bone marrow and spleen showed selective M2-like macrophage and CD8 T-cell changes.