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

JK Holth, SK Fritschi, C Wang, NP Pedersen, JR Cirrito… - Science, 2019 - science.org
JK Holth, SK Fritschi, C Wang, NP Pedersen, JR Cirrito, TE Mahan, MB Finn, M Manis
Science, 2019science.org
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 …
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.
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