2021 Alzheimer's Association Research Grant (AARG)

Curbing Alzheimer’s disease symptoms by robust circadian entrainment

What are the impacts of sleep-wake cycle regulation on onset and progression of Alzheimer’s in the female brain?

Ali Guler, Ph.D.
University of Virginia
Charlottesville, VA - United States

Background

Circadian rhythms are natural biological changes that occur over an approximately twenty-four hour cycle, which is often called the sleep-wake cycle. These rhythms usually respond to the amount of light and darkness in an environment, and they involve daily patterns of sleeping, eating and other activities. Disruptions to circadian rhythms can alter people’s ability to get proper sleep. More than 50% of individuals with dementia experience sleep disruptions or poor sleep patterns that precede cognitive impairment by several years. Past studies suggest that sleep loss may reduce brain function by hindering the ability of brain cells to communicate with each other or by damaging certain brain structures. Dr. Ali Guler and colleagues will study whether regulating circadian rhythms may impact the onset or progression of Alzheimer’s.

Research Plan

Dr. Guler and colleagues will use 2-, 6- and 10-month-old female genetically engineered Alzheimer’s-like mice. The researchers will use female mice because past research shows that cognitive decline and brain changes observed in Alzheimer’s have been extensively studied in these female Alzheimer’s-like mice compared to male Alzheimer’s-like mice.

The researchers will regulate the circadian rhythm of these mice by providing a restricted regimen to food access, voluntary exercise, and light exposure. The research team will study whether the regulation impacts general activity pattern, energy utilization and metabolism in these Alzheimer’s-like mice. Further, Dr. Guler’s team will study whether the regulation of the circadian rhythm is also able to decrease cognitive decline in aging mice.

Finally, the researchers will investigate the impact of circadian rhythm regulation on brain changes in these Alzheimer’s-like mice. Some of these brain changes include - accumulation of beta-amyloid and tau proteins that form plaques and tangles, the two main hallmark brain changes observed in Alzheimer’s. Individuals with Alzheimer’s also typically experience brain inflammation caused by dysregulation of the immune system, which can damage nerve cells. Dr. Guler’s team will study whether the effect of a regulated circadian rhythm on cognition and metabolism, could impact these brain changes in the Alzheimer’s-like mice.

Impact

The study results may help provide insights on whether regulating the circadian clock in the female brain maybe able to delay the onset and progression of Alzheimer’s.