Circadian and Sleep-Wake Dysfunctions of the Hypothalamus in Alzheimer’s Disease Progression

Alzheimer’s disease (AD) is a disorder that causes degeneration of brain cells, cognitive decline, and memory loss. AD is characterized by both the accumulation of tau proteins and the amyloid plaques, which inhibit cell function. Cognitive symptoms are considered manifestations of late-stage AD, though other manifestations such as sleep alterations occur long before these symptoms. Moreover, specific subcortical areas of the brain are affected very early on in AD progression, even before cognitive structures such as the hippocampus. One notable region is the hypothalamus, which regulates circadian rhythms, sleep-wake structure, and other metabolic signals. The hypothalamus is significant in AD progression due to its protective qualities and influence on disease development. This paper investigates the regulation of circadian and sleep-wake cycles within the hypothalamus and how desynchronization may contribute to AD pathogenesis in preclinical and early stages of the disease. Because the hypothalamus is a complex and varied structure, other processes of the hypothalamus are also discussed due to their influence on the sleep-wake cycle. Circadian rhythms also vary among different populations, potentially affecting AD onset. Understanding the influence of circadian and sleep-wake cycles on early AD pathology can provide insight into new interventions and therapeutics preceding later stages of the disease.