Kentucky study links brain immune cells to reversible sleep loss in Alzheimer's mice

University of Kentucky researchers report that microglia, the brain's immune cells, are the main drivers of sleep loss in mice with Alzheimer's-like amyloid plaque pathology, according to SciTechDaily coverage of a study in Alzheimer's & Dementia. Led by Shannon L. Macauley with first author Nicholas J. Constantino, the team found that temporarily eliminating most microglia with the cancer-research drug Pexidartinib (PLX3397) restored more than two hours of sleep each day. After 14 days of treatment, about 87% of the brain's immune cells had been temporarily removed. Sleep improved without a reduction in amyloid plaque burden, pointing to the inflammatory response rather than plaques alone as a reversible driver of disruption. The researchers compared plaque-prone mice with normally aging wild-type mice at six months, when plaques first appeared, and at 18 months. Head-mounted EEG and EMG devices tracked wake, deep sleep, and dreaming sleep. Sleep disruption reached a ceiling early: disruptions at six months did not worsen by 18 months even though plaque burden more than doubled. Aging mainly reduced REM sleep, while Alzheimer's-related pathology selectively disrupted restorative NREM sleep. Macauley's lab is studying ways to quiet microglial overactivity without eliminating the cells, including evaluation of existing medications such as Metformin and Stiripentol. The team also proposes that portable EEG patterns distinguishing Alzheimer's-related pathology from normal aging could support affordable screening. The paper lists DOI 10.1002/alz.71579 and NIH and foundation support including the Cure Alzheimer's Fund and The CART Fund.