Journal article
The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Science (American Association for the Advancement of Science), Vol.363(6429), pp.880-883
02/22/2019
DOI: 10.1126/science.aav2546
PMCID: PMC6410369
PMID: 30679382
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.
Details
- Title: Subtitle
- The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
- Creators
- Jerrah K Holth - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USASarah K Fritschi - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USAChanung Wang - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USANigel P Pedersen - Program in Neuroscience, Emory University, Atlanta, GA 30322, USAJohn R Cirrito - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USAThomas E Mahan - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USAMary Beth Finn - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USAMelissa Manis - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USAJoel C Geerling - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USAPatrick M Fuller - Department of Neurology, Beth Israel Deaconess Medical Center, Division of Sleep Medicine, Harvard Medical School, Boston, MA 02215, USABrendan P Lucey - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USADavid M Holtzman - Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.363(6429), pp.880-883
- DOI
- 10.1126/science.aav2546
- PMID
- 30679382
- PMCID
- PMC6410369
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Publisher
- United States
- Grant note
- R01 NS103161 / NINDS NIH HHS R03 AG047999 / NIA NIH HHS R01 NS092652 / NINDS NIH HHS K08 NS105929 / NINDS NIH HHS K76 AG054863 / NIA NIH HHS UL1 TR002345 / NCATS NIH HHS P01 AG026276 / NIA NIH HHS UL1 TR000448 / NCATS NIH HHS F32 NS089381 / NINDS NIH HHS P01 NS074969 / NINDS NIH HHS KL2 TR002346 / NCATS NIH HHS R01 NS073613 / NINDS NIH HHS P50 AG005681 / NIA NIH HHS KL2 TR000450 / NCATS NIH HHS
- Language
- English
- Date published
- 02/22/2019
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984020611102771
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