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Science. 2019 Jan 24. pii: eaav2546. doi: 10.1126/science.aav2546. [Epub ahead of print]

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

Abstract

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.

PMID:
30679382
DOI:
10.1126/science.aav2546

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