Effect of Sleep on Overnight Cerebrospinal Fluid Amyloid beta Kinetics

Sleep disturbances are associated with future risk of Alzheimer disease. Disrupted sleep increases soluble amyloid beta, suggesting a mechanism for sleep disturbances to increase Alzheimer disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. All participants were infused with C-13(6)- leucine to measure amyloid beta kinetics. We found that sleep deprivation increased overnight amyloid beta 38, amyloid beta 40, and amyloid beta 42 levels by 25 to 30% via increased overnight amyloid b production relative to sleeping controls. These findings suggest that disrupted sleep increases Alzheimer disease risk via increased amyloid b production.