UT San Antonio Receives Grant to Study Circadian Disruption in Alzheimer’s Disease

The University of Texas at San Antonio has been awarded a competitive research grant from the Alzheimer's Association to explore the interaction between genetic and environmental factors and their role in increasing Alzheimer’s disease risk. Set to begin in April, the grant provides $200,000 over three years for the study.

Principal investigator Juan Pablo Palavicini, PhD, an assistant professor in the Department of Cellular and Integrative Physiology and a researcher at the Sam and Ann Barshop Institute for Longevity and Aging Studies, stated that the aim is to integrate various genetic variations and environmental stressors to create a more precise model that reflects late-onset Alzheimer’s disease.

Palavicini is collaborating with Kevin B. Koronowski, PhD, an assistant professor in the Department of Biochemistry and Structural Biology, to primarily investigate the impact of circadian rhythm disruption, considered an environmental stressor, focusing particularly on human phosphorylated-tau proteins. The aggregation of tau proteins and amyloid plaques is recognized as a significant characteristic of Alzheimer’s and other forms of dementia.

Koronowski noted that in today's society, factors like disrupted sleep patterns and poor diet are prevalent, emphasizing that the study seeks to understand the consequences of such disruptions.

In a previous study funded by the William and Ella Owens Medical Foundation, the researchers simulated chronic jet lag in animal models by shifting the light-dark schedule forward by eight hours twice a week. Palavicini compared this effect to traveling multiple time zones in quick succession. In that study, some mice exhibited behavioral changes and metabolic issues, prompting the team to enhance the effects of circadian rhythm disruption in the new study.

To address age-related resilience, the upcoming study will focus on middle-aged subjects and will also incorporate a Western diet high in fat and sugar. Koronowski noted that individuals with irregular work schedules often consume poorer diets, making it essential to consider dietary stress in the context of circadian disruptions.

The research team plans to investigate whether a time-restricted feeding schedule could mitigate metabolic abnormalities caused by circadian disruption. Previous observations indicated that chronic jet lag led to irregular eating patterns, but the new study will implement an automated system limiting food access to a 12-hour window.

Koronowski emphasized the importance of determining whether restoring metabolic rhythms during periods of light disruption can slow Alzheimer’s progression. The study aims to provide a comprehensive understanding of how the misalignment of natural rhythms and homeostasis in the body may contribute to neurodegeneration.

Palavicini highlighted that nighttime is crucial for brain health, as proteins like tau and amyloid beta are cleared during sleep, especially during REM cycles, which are vital for memory consolidation. He noted that even one night of disrupted sleep can significantly affect tau and amyloid levels in the brain.

Findings from this research may offer insights into how environmental factors like disrupted sleep and diet interact with genetic predispositions, potentially clarifying the development of Alzheimer’s in later life. Additionally, the team includes Qing Zhang, MD, and Andrea Gonzalez, a student associate.