Researchers at UT Health San Antonio have secured a grant from the Alzheimer’s Association to investigate the role of circadian rhythm disruptions in the potential development of Alzheimer’s disease. The study will focus on environmental stressors such as jet lag and the consumption of high-fat foods, which may contribute to the disease's risk.
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While about 60% of Alzheimer’s risk is linked to genetics, the remaining factors are less understood and may include environmental influences. Changes in sleep patterns can alter the accumulation of tau and amyloid proteins in the brain, key indicators of Alzheimer’s and other dementias.
Juan Pablo Palavicini, PhD, the principal investigator and assistant professor in the Department of Cellular and Integrative Physiology at the Joe R. and Teresa Long School of Medicine, emphasized the importance of integrating genetic and environmental factors to develop a comprehensive model of late-onset Alzheimer’s. The three-year study, funded with $200,000, is set to begin this month.
Palavicini is collaborating with Kevin B. Koronowski, PhD, an assistant professor in the Department of Biochemistry and Structural Biology, to examine the effects of circadian rhythm disruptions on human phosphorylated-tau proteins. Koronowski noted the challenges of mitigating such disruptions in modern society, highlighting the need for further research into their potential consequences.
The research team previously created an animal model that simulates chronic jet lag by shifting light-dark cycles forward by eight hours twice weekly. In that study, some mice exhibited unusual behaviors and metabolic issues, though the effects were limited. For the upcoming research, Palavicini stated they will use middle-aged subjects and introduce a high-fat Western diet to reflect real-world scenarios often faced by night and rotating shift workers.
The team plans to explore whether a time-restricted feeding schedule could help rectify metabolic abnormalities caused by circadian disruptions. Having noted that chronic jet lag previously led to indiscriminate eating, the new study will implement an automated system that restricts feeding to 12 hours a day.
Koronowski explained that the study aims to clarify whether circadian disruption acts as a cause or effect in the context of neurodegeneration. Understanding how sleep disruptions—especially during critical sleep stages—impact the flushing of harmful proteins may provide insights into Alzheimer’s disease progression.
Additional team members include Qing Zhang, MD, a research scientist, and Andrea Gonzalez, a student associate in Palavicini's lab. Findings from this investigation could enhance understanding of how environmental stressors interact with genetic risks, offering fresh perspectives on the late-onset development of Alzheimer’s.