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

Jae Eun Kang, Miranda M. Lim, Randall J. Bateman, James J. Lee, Liam P. Smyth, John R. Cirrito, Nobuhiro Fujiki, Seiji Nishino, David M. Holtzman

Research output: Contribution to journalArticle

685 Scopus citations

Abstract

Amyloid-β (Aβ) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. Aβ aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of Aβ. Using in vivo microdialysis in mice, we found that the amount of ISF Aβ correlated with wakefulness. The amount of ISF Aβ 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, Aβ 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.

Original languageEnglish (US)
Pages (from-to)1005-1007
Number of pages3
JournalScience
Volume326
Issue number5955
DOIs
StatePublished - Nov 13 2009

ASJC Scopus subject areas

  • General

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    Kang, J. E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009). Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science, 326(5955), 1005-1007. https://doi.org/10.1126/science.1180962