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. The onset and progression of Alzheimer's disease may be associated with sleep cycle disturbance even before cognitive symptoms appear. Alzheimer's disease is a neurodegenerative condition that primarily affects older people, leading to dementia. Disturbed sleep patterns and problems with circadian rhythms, physiological processes which follow a natural 24-hour cycle, are often symptoms of the disease. David Holtzman and co-workers at the Washington University School of Medicine, USA, reviewed research suggesting that sleep disruption may actually occur in the early stages of Alzheimer's disease and exacerbate the disease. The team highlighted research linking sleep cycles with the regulation of certain Alzheimer-related peptides in mouse brains, together with studies connecting neurodegenerative processes with the disruption of circadian rhythms. Therapies targeting sleep disruption could therefore help in the fight against Alzheimer's disease in the future.