Circadian Rhythm Disruption and Alzheimer's Disease

The project investigates how the circadian rhythm disruptions, like chronic jetlag or shiftwork, affect Alzheimer’s disease progression, focusing on amyloid plaques, tau pathology, and inflammation.

This study investigates how disrupted circadian rhythms, common in aging and Alzheimer’s disease (AD), impact disease progression using a mouse model of chronic jetlag (CJL). With two main goals, it aims to understand how CJL affects AD markers—amyloid plaques and tau protein accumulation. Investigating the connection between circadian disruption, glial function, and AD-related changes may reveal therapeutic strategies. Insights gained may offer novel approaches to AD prevention, crucial given the widespread circadian desynchrony in modern society, with implications for public health.

This proposal is unique in its focus on how jetlag, a common modern lifestyle issue, affects Alzheimer’s disease progression by disrupting circadian rhythms. The innovative approach includes using multiple mouse models with varying genetic backgrounds and advanced techniques like single-cell RNA sequencing to comprehensively investigate both amyloid and tau pathology. Additionally, the project integrates the novel use of microglial depletion to determine the role of these cells in circadian disruption and Alzheimer’s pathology.

Circadian rhythm disruption from nighttime light exposure is widespread. Upon completion, this study could offer new insights into how disrupted circadian rhythms modify the Alzheimer’s disease progression, potentially leading to new prevention and treatment strategies. Public awareness of the impact of sleep and daily rhythms on brain health may encourage lifestyle changes that reduce Alzheimer’s risk. For researchers, these findings could open new avenues for targeting circadian mechanisms in Alzheimer’s therapy.