Angelina Kovalchuk

The Role of Circadian and Sleep-Wake Dysfunctions of the Hypothalamus in Alzheimer's Disease Progression

Started Aug. 1, 2023

Abstract or project description

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. However, cognitive symptoms are considered manifestations of late-stage AD, though non-cognitive 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 and other metabolic signals. Both tau and amyloid depositions have been identified very early on in this region. Additionally, sleep and circadian alterations have been consistently observed in AD patients and are speculated to affect the onset of the disease. This review aims to discuss why the hypothalamus is affected early and the extent of its role in the progression of AD. The neuroanatomy, function, and vulnerability of the hypothalamus is important in understanding why and how it is dysregulated in AD. Because the hypothalamus is a complex and varied structure, the focus of this literature review is mostly the regulation of circadian and sleep-wake cycles within the hypothalamus, though other processes of the hypothalamus will also be discussed due to their influence on the sleep-wake cycle. Since circadian rhythms communicate with systems and risk factors involved in the growth and progression of AD, desynchronization of the circadian rhythm may contribute to AD pathogenesis. This review will focus specifically on preclinical and early stages of AD and how disorder of circadian and sleep-wake mechanisms affects pathology in these stages. Understanding the influence of these cycles on early AD pathology can provide insight into new interventions preceding latter stages of the disease.