@article{dbc6037deb294265bb6871d2e67f6826,
title = "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 β-amyloid (Aβ) that accumulates in Alzheimer's disease (AD). Furthermore, chronic sleep deprivation (SD) increases Ab 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.",
author = "Holth, {Jerrah K.} and Fritschi, {Sarah K.} and Chanung Wang and Pedersen, {Nigel P.} and Cirrito, {John R.} and Mahan, {Thomas E.} and Finn, {Mary Beth} and Melissa Manis and Geerling, {Joel C.} and Fuller, {Patrick M.} and Lucey, {Brendan P.} and Holtzman, {David M.}",
note = "Funding Information: This work was supported by a grant from the BrightFocus Foundation (A2017114F, S.K.F.), funding from the Deutsche Forschungsgemeinschaft (3625/1-1, S.K.F.), NIH F32 NS089381 (J.K.H.), NIH K08NS105929 (N.P.P.), NIH R01NS073613 (P.M.F.), R01NS092652 (P.M.F.), NIH P01NS074969 (D.M.H.), the JPB Foundation (D.M.H.), the Tau Consortium (D.M.H.), UL1 TR000448 and KL2 TR000450 (B.P.L.), R03 AG047999 (B.P.L.), K76 AG054863 (B.P.L.), P50 AG05681 (B.P.L.), P01AG26276 (B.P.L.), and the McDonnell Center for Systems Neuroscience at Washington University School of Medicine (B.P.L.). Publisher Copyright: {\textcopyright} The Authors, some rights reserved.",
year = "2019",
doi = "10.1126/science.aav2546",
language = "English",
volume = "363",
pages = "80--884",
journal = "Science",
issn = "0036-8075",
number = "6429",
}