Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics

Ann Neurol. 2018 Jan;83(1):197-204. doi: 10.1002/ana.25117.


Sleep disturbances are associated with future risk of Alzheimer disease. Disrupted sleep increases soluble amyloid β, 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 13 C6 -leucine to measure amyloid β kinetics. We found that sleep deprivation increased overnight amyloid β38, amyloid β40, and amyloid β42 levels by 25 to 30% via increased overnight amyloid β production relative to sleeping controls. These findings suggest that disrupted sleep increases Alzheimer disease risk via increased amyloid β production. Ann Neurol 2018;83:197-204.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Anesthetics / pharmacology
  • Circadian Rhythm
  • Female
  • Humans
  • Kinetics
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Pilot Projects
  • Sleep / physiology*
  • Sleep Wake Disorders / cerebrospinal fluid
  • Sodium Oxybate / pharmacology


  • Amyloid beta-Peptides
  • Anesthetics
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Sodium Oxybate