Alzheimer's Disease, Circadian Rhythms, and the Immune System: Potential Interconnections

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, marked by the accumulation of amyloid-β plaques and neurofibrillary tangles. Its incidence is rising as the global population ages. This narrative review explores the emerging interconnections among AD, circadian rhythms, and the immune system. The circadian system, governed by endogenous clocks, regulates key physiological processes and exhibits disruptions in the early stages of AD. Chronodisruption, disturbance of circadian rhythms, has been implicated in AD pathogenesis through its effects on metabolism, sleep, and neuroinflammation. The immune system also plays a central role in AD, with microglia and astrocytes contributing to disease progression. Immune function displays circadian variation, and disruptions in sleep and circadian timing may impair immune responses, promote inflammation, and compromise amyloid-β clearance. Therapeutic strategies targeting circadian regulation, including melatonin agonists and orexin receptor antagonists, may help mitigate cognitive decline. Additionally, the gut microbiome, modulated by circadian and sleep patterns, has emerged as a potential contributor to AD pathophysiology. This review also highlights interventions that support immune health, such as the Mediterranean diet, antiviral therapies, and physical activity, which may collectively attenuate AD risk. Finally, the bidirectional relationship between immune signaling and circadian rhythms, evidenced by immune modulation of clock genes, underscores a complex, integrated regulatory network. Understanding these interrelated systems may uncover novel approaches for prevention and treatment. By elucidating these interconnections, this review aims to shed light on novel therapeutic strategies and interventions that address multiple facets of the disease, offering potential avenues to improve outcomes for individuals with AD.