Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease

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• 作者：Jonathan Cedernaes^a ; ^{Jonathan.Cedernaes@neuro.uu.se} ; Ricardo S. Osorio^b ; ^{Ricardo.Osorio@nyumc.org} ; Andrew W. Varga^c ; Korey Kam^c ; Helgi B. Schiö ; th^a ; Christian Benedict^a ; ^{Christian.Benedict@neuro.uu.se}
• 关键词：Aging ; Amyloid beta ; Blood brain barrier ; Circadian misalignment ; Neurodegeneration ; Orexin ; Oxidative stress ; Sleep disruption ; Slow-wave sleep ; Tau
• 刊名：Sleep Medicine Reviews
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：31
• 期：Complete
• 页码：102-111
• 全文大小：1208 K
• 卷排序：31

文摘

During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood–brain barrier function – conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.