Circadian Clock Gene Dysregulation in Alzheimer’s Disease: Insights and Implications

Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is increasingly understood to involve not just traditional neuropathological hallmarks but also disruptions in systemic physiological processes, notably the circadian rhythms. The intersection of circadian clock gene dysregulation and the pathogenesis of AD, emphasizing both the insights gained and the potential therapeutic implications. Circadian rhythms, which govern daily physiological and metabolic processes, are regulated by core clock genes such as  BMAL1, PER, CRY, and others. In AD, multiple studies have observed altered expression and function of these genes, which may contribute to the characteristic symptoms of the disease, including disrupted sleep patterns, changes in daily activity levels, and mood fluctuations. circadian dysfunction might exacerbate AD pathology through mechanisms such as increased amyloid-beta production, impaired clearance, and neuroinflammation. Furthermore, targeting circadian clock genes and their regulatory pathways might offer novel strategies for AD management, such as the timing of drug administration to coincide with optimal circadian phases, or the use of chronotherapeutics. Finally,  identifing gaps in current knowledge and suggests directions for future research to better understand the role of circadian biology in AD and to harness this information for therapeutic benefit. This review not only underscores the importance of circadian rhythms in AD but also highlights the potential for circadian-based interventions to mitigate disease progression and improve quality of life for affected individuals.