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

ABSTRACT: The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of ?-amyloid (A?) that accumulates in Alzheimer's disease (AD). Furthermore, chronic sleep deprivation (SD) increases A? plaques. However, tau, not A?, 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 A? and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading.

SUBMITTER: Holth JK 

PROVIDER: S-EPMC6410369 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature