Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease

Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep-wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep-wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD.