University of Kentucky researchers report that overactive microglia, the brain's immune cells, drive sleep loss in a mouse model of Alzheimer's disease. Depleting about 87% of them with the drug pexidartinib (PLX3397) for 14 days gave the mice more than two hours of extra sleep per day.
Sleep disruption was already present at 6 months and did not worsen by 18 months, even though plaque burden more than doubled. Alzheimer's pathology selectively disrupted deep NREM sleep, while normal aging mainly reduced REM sleep. Sleep improved without any reduction in amyloid plaques. The study, led by Shannon Macauley and Nicholas Constantino, appears in Alzheimer's & Dementia.
The result is preclinical. Removing most microglia is not a practical treatment because the cells also protect the brain, so the team is exploring ways to modulate them instead. A proposed EEG biomarker for early detection still needs validation in humans.