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


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.

SUBMITTER: Kang JE 

PROVIDER: S-EPMC2789838 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Kang Jae-Eun JE   Lim Miranda M MM   Bateman Randall J RJ   Lee James J JJ   Smyth Liam P LP   Cirrito John R JR   Fujiki Nobuhiro N   Nishino Seiji S   Holtzman David M DM  

Science (New York, N.Y.) 20090924 5955


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  ...[more]

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