Circadian alterations in patients with neurodegenerative diseases: Neuropathological basis of underlying network mechanisms.

Circadian organization of physiology and behavior is an important biological process that allows organisms to anticipate and prepare for daily changes and demands. Disruptions in this system precipitates a wide range of health issues. In patients with neurodegenerative diseases, alterations of circadian rhythms are among the most common and debilitating symptoms. Although a growing awareness of these symptoms has occurred during the last decade, their underlying neuropathophysiological circuitry remains poorly understood and consequently no effective therapeutic strategies are available to alleviate these health issues. Recent studies have examined the neuropathological status of the different neural components of the circuitry governing the generation of circadian rhythms in neurodegenerative diseases. In this review, we will dissect the potential contribution of dysfunctions in the different nodes of this circuitry to circadian alterations in patients with neurodegenerative diseases. A deeper understanding of these mechanisms will provide not only a better understanding of disease neuro-pathophysiology, but also hold the promise for developing effective and mechanisms-based therapies.