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, 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
Abstract
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 Aβ and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading.
Conflict of interest statement
Competing interests: D.M.H. co-founded and is on the scientific advisory board of C2N Diagnostics. D.M.H. is on the scientific advisory board of Denali, Genentech, and Proclara. D.M.H. consults for AbbVie. None of the authors report competing interests.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Source: PubMed