- Sleep dynamically shapes microglial functions, regulating neuroinflammatory tone, metabolic waste clearance and synaptic remodelling to support proteostasis.
- Failure of the sleep-microglia axis may impair homeostatic functions and contribute to Alzheimer’s disease onset and progression.
- Preclinical and clinical data suggest sleep-targeting interventions could recalibrate microglial homeostasis and slow Alzheimer’s disease progression.
Trends Neurosci. 2026 Sep 22:S0166-2236(26)00187-6. doi: 10.1016/j.tins.2026.09.005. Online ahead of print.
ABSTRACT
Sleep is a fundamental regulator of brain homeostasis, yet how distinct brain cell types contribute to this process remains poorly understood. Microglia, the resident immune cells of the central nervous system, actively regulate neuroinflammatory tone, metabolic waste clearance, and synaptic remodeling, thereby contributing to neural circuit maintenance and proteostasis. Delineating the different functions played by microglia during specific brain states, such as sleep, represents an active area of research. In this article, we review a growing literature supporting the notion that sleep dynamically shapes microglial functional outputs. We further suggest that the failure of the sleep-microglia axis may represent an important component of the molecular framework of Alzheimer’s disease (AD), contributing to disease progression. Finally, we discuss preclinical and clinical evidence suggesting that sleep-targeting interventions may modulate AD pathology, and highlight the possibility that restoring sleep physiology could recalibrate microglial homeostatic functions and slow disease progression.
PMID:42850105 | DOI:10.1016/j.tins.2026.09.005
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