Sleep and Alzheimer's disease: A pivotal role for the suprachiasmatic nucleus

Alzheimer's disease (AD), which accounts for most of the dementia cases, is, aside from cognitive deterioration, often characterized by the presence of non-cognitive symptoms. Society is desperately in need for interventions that alleviate the economic and social burden related to AD. Circadian dysrhythmia, one of these symptoms in particular, immensely decreases the self-care ability of AD patients and is one of the main reasons of caregiver exhaustion. Studies suggest that these circadian disturbances form the root of sleep-wake problems, diagnosed in more than half of AD patients. Sleep abnormalities have generally been considered merely a consequence of AD pathology. Recent evidence suggests that a bidirectional relationship exists between sleep and AD, and that poor sleep might negatively impact amyloid burden, as well as cognition. The suprachiasmatic nucleus (SCN), the main circadian pacemaker, is subjected to several alterations during the course of the disease. Its functional deterioration might fulfill a crucial role in the relation between AD pathophysiology and the development of sleep abnormalities. This review aims to give a concise overview of the anatomy and physiology of the SCN, address how AD pathology precisely impacts the SCN and to what degree these alterations can contribute to the progression of the disease.