Brain perivascular macrophages regulate endothelial cell function via a cMAF-dependent transcriptional program in mouse and human.

cMAF is the key transcription factor in brain perivascular macrophages, and conditional deletion disrupts their phenotype in vivo, with downstream effects on cerebral arteries.

• Why it matters: Perivascular macrophages support brain physiology, but the transcriptional regulators and how they shape endothelial and vascular function in health and Alzheimer’s disease are unclear.
• What they did: Using single-cell multi-omics plus functional experiments, the study links cMAF to IGF1 expression in perivascular macrophages and tests effects of cMAF deletion on cerebral arteries; it also analyzes human macrophages and AD.
• The result: cMAF deletion alters cerebral artery transcription and vascular functions, while in human AD perivascular macrophages upregulate cMAF and IGF1, a response abrogated in APOE4 carriers; a cMAF polymorphism suggests the cMAF program is protective against AD.

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