| First Author | Holth JK | Year | 2019 |
| Journal | Science | Volume | 363 |
| Issue | 6429 | Pages | 880-884 |
| PubMed ID | 30679382 | Mgi Jnum | J:295802 |
| Mgi Id | MGI:6454480 | Doi | 10.1126/science.aav2546 |
| Citation | Holth JK, et al. (2019) The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans. Science 363(6429):880-884 |
| abstractText | The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of beta-amyloid (Abeta) that accumulates in Alzheimer's disease (AD). Furthermore, chronic sleep deprivation (SD) increases Abeta plaques. However, tau, not Abeta, 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 Abeta and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading. |
