Yves Dauvilliers^{a, b}

^a National Reference Centre for Orphan Diseases, Narcolepsy – Rare Hypersomnias, Sleep Unit, Department of Neurology, CHU Montpellier, University of Montpellier, Montpellier, France; 
^b Institute for Neurosciences of Montpellier INM, University of Montpellier, INSERM, Montpellier, France

© 2021 The Author(s)
Published by S. Karger AG, Basel

• Chapter 12 graphical abstract

Advances in translational research provide key opportunities to explore the physiological and pathological effects of sleep in different neurodegenerative diseases. Recent findings suggest that sleepwakefulness dysfunctions may predispose to neurodegenerative disorders such as Alzheimer’s disease (AD), and vice versa. New theories on the link between sleep and β-amyloid and tau secretion, accumulation and clearance, and its interaction with hypocretins/orexins (key neuropeptides regulating wakefulness) suggest mechanistic ways to better understand the impact of sleep alterations in the pathogenesis of AD. Further studies should validate whether changes in circadian rhythm and sleepwakefulness patterns could be used for early AD diagnosis and as prognostic markers for cognitive decline. Longitudinal studies are needed, not only to validate these biomarker interactions and to determine the cause-effect relationship and the role of sleep-wakefulness behavior in the regulation of amyloid plaque and neurofibrillary tangle formation, but also to identify the best sleep therapies and related preventive strategies for AD.

• Sleep disturbances may predispose to neurodegenerative disorders such as AD.
• The link between sleep and Aβ and tau secretion, accumulation, and clearance and its interaction with hypocretins/orexins suggest mechanistic ways to better understand the impact of sleep alterations in the pathogenesis of AD.
• Further studies are required to determine whether managing sleep problems and increasing slow-wave sleep may alter amyloid plaque and neurofibrillary tangle formation, and thus prevent the risk of dementia.
• The effects of orexin receptor antagonists on nighttime sleep and, consequently, on the reduction in the accumulation of Aβ and tau deserve to be studied in detail in subjects at risk of developing AD.

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