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Science. 2009 Nov 13;326(5955):1005-7. doi: 10.1126/science.1180962. Epub 2009 Sep 24.

Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.

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  • 1Department of Neurology, Washington University, St. Louis, MO 63110, USA.

Abstract

Amyloid-beta (Abeta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. Abeta aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of Abeta. Using in vivo microdialysis in mice, we found that the amount of ISF Abeta correlated with wakefulness. The amount of ISF Abeta also significantly increased during acute sleep deprivation and during orexin infusion, but decreased with infusion of a dual orexin receptor antagonist. Chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, Abeta plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer's disease.

PMID:
19779148
[PubMed - indexed for MEDLINE]
PMCID:
PMC2789838
Free PMC Article

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