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Brain border-associated macrophages rhythmically scavenge amyloid-beta and regulate vascular amyloid pathology

ABSTRACT: Circadian disruptions perturb the brain and immune system and increase the risk of developing Alzheimer’s Disease (AD), yet whether this involves dysregulation of brain immunity remains less clear. Here, we perform single-cell RNA sequencing of the brain immune compartment around the day-night cycle and identify brain border-associated macrophages (BAMs) as highly rhythmic cells. We find that the rest phase is a specialized time for BAM engulfment, characterized by upregulation of endocytic machinery and enhanced uptake of extracellular fluid-borne material including amyloid-beta (Aβ). Rhythmicity in BAM scavenging is regulated by the clock gene Bmal1, mediated by the endocytic receptor CD206, and perturbed with age. In a mouse model of AD, deletion of Bmal1 in BAMs worsens perivascular and leptomeningeal Aβ plaque burden. Our results characterize rapid endocytosis of fluid-borne substrates as a specialized and rhythmic BAM function and identify perturbed timing of brain border immune function as one potential avenue by which circadian disruptions may precipitate amyloidosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE347334 | GEO | 2026/09/20

REPOSITORIES: GEO

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CLK:BMAL1 is a pioneer-like transcription factor [MNase-Seq]

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