Misalignment or fragmentation of circadian rhythms can promote numerous diseases, from diabetes to cancer, and may accelerate brain aging and Alzheimer’s disease (AD). Disruption of circadian rhythms is a major symptom of AD, which occurs very early in the disease course and contributes to sleep dysfunction and cognitive problems such as sundowning. Recent findings from our lab and others show that disrupting circadian rhythms has strong effects on brain pathology in mouse models of AD, suggesting that impaired circadian function may contribute to AD risk and pathology. However, it is unknown whether enhancing circadian rhythms can protect the brain from AD.
In this proposal, we will test the hypothesis that strengthening circadian rhythms, even in mice with normal rhythmicity at baseline, will prevent several different aspects of AD pathology in mouse models, including amyloid and tau aggregation, inflammation, sleep disturbances, and neurodegeneration. Our collaborative efforts will allow us to test the effects of circadian enhancement on a variety of AD-related pathologies, to examine the relationship between circadian rhythm strength and risk of developing AD pathology in humans, and to test a novel drug for enhancing circadian rhythms. Together, these studies will help determine if enhancement of circadian rhythms might be a therapeutic strategy to prevent AD.
