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Science. 2019 Feb 22;363(6429):880-884. doi: 10.1126/science.aav2546. Epub 2019 Jan 24.

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

Author information

1
Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Neurology, Emory Epilepsy Center, Emory University, Atlanta, GA 30322, USA.
4
Program in Neuroscience, Emory University, Atlanta, GA 30322, USA.
5
Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
6
Department of Neurology, Beth Israel Deaconess Medical Center, Division of Sleep Medicine, Harvard Medical School, Boston, MA 02215, USA.
7
Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. holtzman@wustl.edu.
#
Contributed equally

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.

PMID:
30679382
PMCID:
PMC6410369
[Available on 2020-02-22]
DOI:
10.1126/science.aav2546

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