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Dysfunction of circadian and sleep rhythms is an early feature of many neurodegenerative diseases. Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in cognitive and psychiatric disturbances. Although it is largely unclear whether dysfunctions in sleep and circadian rhythms contribute to the etiology of AD or are a consequence of the disease, there is evidence that these conditions are involved in a complex self-reinforcing bidirectional relationship. According to the recent studies, dysregulation of the circadian clock already occurs during the asymptomatic stage of the disease and could promote neurodegeneration. Thus, restoration of sleep and circadian rhythms in preclinical AD may represent an opportunity for early intervention to slow the disease course.

Humans and other mammalian species possess an endogenous circadian clock system that has evolved in adaptation to periodically reoccurring environmental changes and drives rhythmic biological functions, as well as behavioural outputs with an approximately 24-hour period. In mammals, body clocks are hierarchically organized, encompassing a so-called pacemaker clock in the hypothalamic suprachiasmatic nucleus (SCN), non-SCN brain and peripheral clocks, as well as cell-autonomous oscillators within virtually every cell type. A functional clock machinery on the molecular level, alignment among body clocks, as well as synchronization between endogenous circadian and exogenous environmental cycles has been shown to be crucial for our health and well-being. Yet, modern life constantly poses widespread challenges to our internal clocks, for example artificial lighting, shift work and trans-meridian travel, potentially leading to circadian disruption or misalignment and the emergence of associated diseases. For instance many of us experience a mismatch between sleep timing on work and free days (social jetlag) in our everyday lives without being aware of health consequences that may arise from such chronic circadian misalignment, Hence, this review provides an overview of the organization and molecular built-up of the mammalian circadian system, its interactions with the outside world, as well as pathologies arising from circadian disruption and misalignment.