| Literature DB >> 30679382 |
Jerrah K Holth1,2, Sarah K Fritschi1,2, Chanung Wang1,2, Nigel P Pedersen3,4, John R Cirrito1,2, Thomas E Mahan1,2, Mary Beth Finn1,2, Melissa Manis1,2, Joel C Geerling5, Patrick M Fuller6, Brendan P Lucey1,2, David M Holtzman7,2.
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.Entities:
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Year: 2019 PMID： 30679382 PMCID： PMC6410369 DOI： 10.1126/science.aav2546
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728