睡眠-觉醒周期调节小鼠脑间质液 tau 和人类 CSF tau。
The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans.
机构信息
Department of Neurology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
出版信息
Science. 2019 Feb 22;363(6429):880-884. doi: 10.1126/science.aav2546. Epub 2019 Jan 24.
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.
睡眠-觉醒周期调节β-淀粉样蛋白（Aβ）在阿尔茨海默病（AD）中的细胞外液（ISF）和脑脊液（CSF）水平。此外，慢性睡眠剥夺（SD）会增加 Aβ斑块。然而，似乎是 tau 而不是 Aβ 的积累导致了 AD 的神经退行性变。我们测试了睡眠-觉醒周期和 SD 是否会影响 ISF/CSF tau 和 tau 播散。与睡眠相比，正常觉醒时小鼠 ISF tau 增加了约 90%，而 SD 时增加了约 100%。人类 CSF tau 在 SD 期间也增加了超过 50%。在 tau 播散模型中，慢性 SD 增加了 tau 病理学的播散。化学诱导的小鼠清醒也显著增加了 ISF Aβ 和 tau。因此，睡眠-觉醒周期调节 ISF tau，SD 增加 ISF 和 CSF tau 以及 tau 病理学的播散。
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