Cited by 817Alzheimer's disease research and treatmentsSleep and Wakefulness ResearchCerebrospinal fluid and hydrocephalus

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

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Holth, Jerrah K., Fritschi, Sarah K., Wang, Chanung, Pedersen, Nigel P., Cirrito, John R., Mahan, Thomas E., Finn, Mary Beth, Manis, Melissa, Geerling, Joel C., Fuller, Patrick M., Lucey, Brendan P., Holtzman, David M.·2019·Science

DOI 10.1126/science.aav2546PMC PMC6410369

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Abstract

Sleep may protect the brain from AD: Two main proteins accumulate in the brain in Alzheimer's disease (AD), β-amyloid (Aβ) and tau. Aβ appears to instigate AD, but tau appears to drive brain damage and cognitive decline. Sleep deprivation is known to increase Aβ acutely and chronically. Now, Holth et al. show that chronic sleep deprivation strongly increases tau acutely over hours and also drives tau pathology spreading in the brains of mice and humans (see the Perspective by Noble and Spires-Jones). Thus, sleep appears to have a direct protective effect on a key protein that drives AD pathology. Science , this issue p. 880 ; see also p. 813

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“As neuronal synaptic strength/connectivity is higher during wakefulness than during sleep (11, 12), we asked whether tau levels in the brain interstitial fluid (ISF) varied with the sleep-wake cycle.”
Background
Neuronal activity enhances tau propagation and tau pathology in vivo
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Authors: Holth, J. K., Fritschi, S. K., Wang, C., Pedersen, N. P., Cirrito, J. R., Mahan, T. E., Finn, M. B., Manis, M., Geerling, J. C., Fuller, P. M., Lucey, B. P., & Holtzman, D. M.
Affiliations: Washington University in St. Louis (US)
Emory University (US)
University of Iowa Hospitals and Clinics (US)
Beth Israel Deaconess Medical Center (US)
Corresponding author: Holth, Jerrah K.
Fritschi, Sarah K.
Holtzman, David M.
ORCID: Holth, Jerrah K.
Fritschi, Sarah K.
Wang, Chanung
Pedersen, Nigel P.
Cirrito, John R.
Mahan, Thomas E.
Finn, Mary Beth
Manis, Melissa
Geerling, Joel C.
Fuller, Patrick M.
Lucey, Brendan P.
Holtzman, David M.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2019-02-22
Volume: 363
Issue: 6429
Pages: 880-884
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.aav2546
PMC: PMC6410369
OpenAlex: W2912003143
Cited by: 813
References: 33
Citations by year: 2026: 117 · 2025: 121 · 2024: 128 · 2023: 115 · 2022: 98 · 2021: 98 · 2020: 87 · 2019: 49
FWCI: 56.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institute on Aging (AG047999, AG054863, AG05681, AG26276)
National Institute of Neurological Disorders and Stroke (NS074969, NS073613, K08NS105929, NS089381)
National Center for Advancing Translational Sciences (TR000448, TR000450)
BrightFocus Foundation (A2017114F)
Deutsche Forschungsgemeinschaft (3625/1-1)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
Keywords: sleep-wake cycle, tau protein, cerebrospinal fluid, interstitial fluid, chronic sleep deprivation, Alzheimer's disease, amyloid-beta, tau pathology
MeSH terms: Animals, Brain, Circadian Rhythm, Female, Male, Mice, Transgenic, Sleep, Sleep Deprivation, Wakefulness, Amyloid beta-Peptides, tau Proteins, Extracellular Fluid, Mice

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

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