bioRxiv : the preprint server for biologyDec 22, 2025

The body’s internal clock controls how brain border immune cells clear waste from fluid

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Brain border macrophages showed circadian timing of fluid scavenging that may influence amyloid-beta buildup in aging and AD models.

Evidence

This mouse single-cell and functional study profiled brain immune cells across the day-night cycle and tested BAM uptake, Bmal1 regulation, CD206 involvement, aging effects, and Abeta plaque burden in an AD model.

Caveat

The evidence comes from mouse and model-system experiments, with the abstract indicating a potential mechanism rather than direct human evidence that circadian disruption causes amyloidosis.

Simplified

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. During the rest phase, we find that BAMs exhibit coordinated upregulation of endocytic genes and enhanced uptake of extracellular fluid-borne material including amyloid-beta (Aβ). Rhythmicity in BAM scavenging is regulated by the clock gene, mediated by the endocytic receptor CD206, and perturbed with age. In a mouse model of AD, we show that deletion ofin BAMs worsens perivascular and leptomeningeal Aβ plaque burden. Our results identify endocytosis as a specialized and rhythmic BAM function and identify perturbed timing of brain border immune functions as a potential mechanism by which circadian disruptions precipitate amyloidosis. Bmal1Bmal1