Exercise-boosted muscle vesicles reprogram microglia to clear amyloid in Alzheimer’s mice

Swim-based exercise increases skeletal muscle-derived extracellular vesicles (SKM-EVs) that are taken up by brain microglia, promoting a disease-associated microglia phenotype and enhanced clearance of amyloid-beta plaques; the EV cargo miR-378a-3p modulates lipid metabolism by targeting p110α, and delivering miR-378a-3p–overexpressing EVs alleviates cognitive impairment in APP/PS1 mice, suggesting a muscle-to-brain myokine mechanism and a potential exercise-mimetic therapy for Alzheimer’s disease.