Interplay between circadian rhythms and epigenetics in neural stem cells and Alzheimer’s disease

The circadian clock, as a molecular timekeeper, influences most behavioural and physiological processes. Numerous symptoms associated with neurodegenerative diseases, such as sleep disorders, anxiety, and mood alteration, are linked to circadian clock dysregulation. Dysregulation of the circadian system is increasingly implicated in the onset and progression of Alzheimer's disease, and emerging evidence highlights a bidirectional relationship between Alzheimer’s disease and circadian clock disruption. A crucial point is that the circadian clock regulates adult neurogenesis, a process that is significantly impaired in Alzheimer’s disease. Recent advancements suggest that the dynamic epigenetic mechanisms—including DNA and histone modifications as well as regulation by non-coding RNA—act as a critical regulation for circadian rhythms and neurogenesis. Therefore, research on circadian disruption and, particularly, focus on harmonising the circadian clock with neurogenesis in neurodegenerative diseases may also speed up the creation of innovative, circadian-based treatments to counteract the progress of neurological disorders from a new perspective. In this review, we explore potential epigenetic mechanisms linking the circadian system to neurodegenerative diseases, with a focus on Alzheimer’s Disease.