. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009 Nov 13;326(5955):1005-7. PubMed.


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  1. In this work from Dave Holtzman’s lab, the influence of the sleep-wake cycle on Aβ metabolism was explored. The investigators found that brain interstitial fluid levels of Aβ in transgenic mice fluctuated over a 24-hour period with lower levels during sleep and higher levels during wakefulness. Moreover, sleep-depriving the mice caused an increase in plaque load, but this effect could be abolished by treating the mice with Almorexant, a receptor antagonist of orexin—a molecule regulating the sleep-wake cycle. Finally, the researchers also looked at human CSF Aβ levels and found similar alterations over the day. This study provides important new evidence that Aβ formation and plaque deposition can be controlled by affecting the sleep pattern. Also, the work adds a new perspective to the use of CSF Aβ as a diagnostic marker, as the reference values may have to be adjusted to the sampling timepoints.