The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans

The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ) that accumulates in Alzheimer's disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Human CSF tau also increased more than 50% during SD. In a tau seeding-and-spreading model, chronic SD increased tau pathology spreading. Chemogenetically driven wakefulness in mice also significantly increased both ISF…

• EL
  Eli Lilly and Company
• BF
  BrightFocus Foundation

  Award: A2017114F
• DF
  Deutsche Forschungsgemeinschaft

  Award: 3625/1-1
• NI
  National Institutes of Health

  Awards: UL1 TR000448, P50 AG05681, TR000448, R01NS092652, K76 AG054863, P01NS074969, AG05681, K08NS105929, R01NS073613, KL2 TR000450, R03 AG047999, P01 AG26276
• MC
  McDonnell Center for Systems Neuroscience

  Award: UL1 TR000448
• NI
  National Institute on Aging

  Awards: AG047999, AG054863, AG05681, AG26276
• NI
  National Institute of Neurological Disorders and Stroke

  Awards: K08NS105929, NS074969, NS089381, NS073613
• NC
  National Center for Advancing Translational Sciences

  Awards: TR000450, TR000448