UK researchers find brain immune cells drive sleep loss in Alzheimer’s

A University of Kentucky study suggests sleep loss in Alzheimer’s is caused not by brain plaques directly, but by the immune cells that respond to them.

Researchers compared it to sprinklers flooding a house to put out a small kitchen fire. In the brain, amyloid plaques are the fire, and microglia — the brain’s immune cells — are the sprinklers. The response meant to protect ends up disrupting sleep.

Published in Alzheimer’s & Dementia, the study led by Dr. Shannon L. Macauley found that microglia trigger inflammation that keeps the brain awake. “It is not the plaques themselves… that cause sleep loss but actually microglia,” Macauley said.

In tests with mice, the team temporarily removed 87% of microglia using a cancer drug, Pexidartinib. The Alzheimer’s mice then gained more than two hours of sleep per night, with longer periods of restorative NREM sleep. This happened without reducing plaque levels.

The researchers also found a “ceiling effect.” Sleep disruption was worst when plaques first appeared and didn’t worsen as plaques increased, suggesting the initial immune reaction causes the damage.

The team now hopes to use portable EEG to detect these changes early and test existing drugs like Metformin to calm microglia instead of removing them. “If we can target that process, it might help with quality of life, attention, cognition and confusion,” Macauley said.