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 b-amyloid (Ab) that accumulates in Alzheimer’s disease (AD). Furthermore, chronic
sleep deprivation (SD) increases Ab plaques. However, tau, not Ab, 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 Ab and tau. Thus, the sleep-wake cycle regulates ISF
tau, and SD increases ISF and CSF tau as well as tau pathology spreading.
http://science.sciencemag.org/content/363/6429/880