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

Jerrah K. Holth, Sarah K. Fritschi, Chanung Wang, Nigel P. Pedersen, John R. Cirrito, Thomas E. Mahan, Mary Beth Finn, Melissa Manis, Joel C. Geerling, Patrick M. Fuller, Brendan P. Lucey, David M. Holtzman. Science 2019 Read More


The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal (CSF) levels of amyloid-β (Aβ) that accumulates in Alzheimer disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. Here, we tested whether ISF/CSF tau and tau seeding/spreading was influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness vs. sleep and ~100% during SD. Human CSF tau also increased over 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 Aβ and tau. Thus, the sleep-wake cycle regulates ISF tau and sleep deprivation increases ISF and CSF tau as well as tau pathology spreading. © 2019, American Association for the Advancement of Science. All Rights Reserved.

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Posted on February 28, 2019
Posted in: Clocks & Sleep, HPAN, Neurodegeneration, Publications Authors: , ,