Astrocytic cholesterol jams brain clearance in AD

Nature Neuroscience, Published online: 05 May 2026; doi:10.1038/s41593-026-02310-3

Zhang and colleagues identify astrocytic calcium–cholesterol–AQP4 signaling that drives glymphatic dysfunction in early Alzheimer’s disease (AD). Attenuating this signaling restored glymphatic flow, reduced amyloid burden and improved cognition in young 5xFAD mice only when glymphatic perfusion and lymphatic drainage were intact. These findings position astrocytic metabolic state as a determinant of brain waste clearance and a potential therapeutic target in early AD.