Author: Wang, Chanung; Holtzman, David M.
Description: As we age, we experience changes in our nighttime sleep and daytime wakefulness. Individuals afflicted with Alzheimer’s disease (AD) can develop sleep problems even before memory and other cognitive deficits are reported. As the disease progresses and cognitive changes ensue, sleep disturbances become even more debilitating. Thus, it is imperative to gain a better understanding of the relationship between sleep and AD pathogenesis. We postulate a bidirectional relationship between sleep and the neuropathological hallmarks of AD; in particular, the accumulation of amyloid-B (AB) and tau. Our research group has shown that extracellular levels of both AB and tau fluctuate during the normal sleep-wake cycle. Disturbed sleep and increased wakefulness acutely lead to increased AB production and decreased AB clearance, whereas AB aggregation and deposition is enhanced by chronic increased wakefulness in animal models. Once AB accumulates, there is evidence in both mice and humans that this results in disturbed sleep. New findings from our group reveal that acute sleep deprivation increases levels of tau in mouse brain interstitial fluid (ISF) and human cerebrospinal fluid (CSF) and chronic sleep deprivation accelerates the spread of tau protein aggregates in neural networks. Finally, recent evidence also suggests that accumulation of tau aggregates in the brain correlates with decreased nonrapid eye movement (NREM) sleep slow wave activity. In this review, we first provide a brief overview of the AD and sleep literature and then highlight recent advances in the understanding of the relationship between sleep and AD pathogenesis. Importantly, the effects of the bidirectional relationship between the sleep-wake cycle and tau have not been previously discussed in other reviews on this topic. Lastly, we provide possible directions for future studies on the role of sleep in AD.
Subject headings: Aging; Alzheimer Disease; Amyloid beta-Peptides; Animals; Humans; Sleep; Sleep Wake Disorders; tau Proteins
Publication year: 2020
Journal or book title: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Volume: 45
Issue: 1
Pages: 104-120
Find the full text: https://www.strategian.com/fulltext/Wang2020.pdf
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Serial number: 4076
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