期刊
SCIENCE
卷 326, 期 5955, 页码 1005-1007出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1180962
关键词
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资金
- NIH [AG025824, AG030946, NS065667, AG029524, MH072525]
- Neuroscience Blueprint Center Core [P30 NS057105]
- Cure Alzheimer's Fund
- Alzheimer's Association Zenith Award
- Eli Lilly
Amyloid-beta (A beta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. A beta aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of A beta. Using in vivo microdialysis in mice, we found that the amount of ISF A beta correlated with wakefulness. The amount of ISF A beta 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, A beta 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.
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