Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2019-02, Vol.363 (6429), p.880-884

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2019

Quelle

Science Online_科学在线

Beschreibungen/Notizen

• 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.