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Sleep and Alzheimer disease pathology—a bidirectional relationship


Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-β (Aβ) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep–wake cycle directly influences levels of Aβ in the brain. In experimental models, sleep deprivation increases the concentration of soluble Aβ and results in chronic accumulation of Aβ, whereas sleep extension has the opposite effect. Furthermore, once Aβ accumulates, increased wakefulness and altered sleep patterns develop. Individuals with early Aβ deposition who still have normal cognitive function report sleep abnormalities, as do individuals with very mild dementia due to AD. Thus, sleep and neurodegenerative disease may influence each other in many ways that have important implications for the diagnosis and treatment of AD.

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Figure 1: The bidirectional relationship between sleep and AD.


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The authors' work is supported by NIH grant P01NS074969 and the Ellison Medical Foundation Senior Scholar Award (both to D. M. Holtzman). The research described in this article was made possible by a grant to Y. S. Ju from the National Center for Research Resources (UL1 RR024992), which is a component of the NIH, and the NIH Roadmap for Medical Research.

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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission.

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Correspondence to David M. Holtzman.

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Competing interests

D. M. Holtzman is a co-founder and member of the scientific advisory board of C2N Diagnostics. He also acts as a consultant for Genentech and AstraZeneca, and his laboratory receives research grants from AstraZeneca and Eli Lilly. These interests are not related to the topic of this article. The other authors declare no competing interests.

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Ju, YE., Lucey, B. & Holtzman, D. Sleep and Alzheimer disease pathology—a bidirectional relationship. Nat Rev Neurol 10, 115–119 (2014).

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