Circadian dysregulation and Alzheimer’s disease: A comprehensive review

Abstract

Alzheimer’s disease (AD), the foremost variant of dementia, has been associated with a menagerie of risk factors, many of which are considered to be modifiable. Among these modifiable risk factors is circadian rhythm, the chronobiological system that regulates sleep‐wake cycles, food consumption timing, hydration timing, and immune responses amongst many other necessary physiological processes. Circadian rhythm at the level of the suprachiasmatic nucleus (SCN), is tightly regulated in the human body by a host of biomolecular substances, principally the hormones melatonin, cortisol, and serotonin. In addition, photic information projected along afferent pathways to the SCN and peripheral oscillators regulates the synthesis of these hormones and mediates the manner in which they act on the SCN and its substructures. Dysregulation of this cycle, whether induced by environmental changes involving irregular exposure to light, or through endogenous pathology, will have a negative impact on immune system optimization and will heighten the deposition of Aβ and the hyperphosphorylation of the tau protein. Given these correlations, it appears that there is a physiologic association between circadian rhythm dysregulation and AD. This review will explore the physiology of circadian dysregulation in the AD brain, and will propose a basic model for its role in AD‐typical pathology, derived from the literature compiled and referenced throughout.