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2016 Grants - Todd
A Circadian Circuit for Behavioral Aggression in Alzheimer's Disease
William David Todd, Ph.D.
Beth Israel Deaconess Medical Center
2016 Alzheimer’s Association Research Fellowship (AARF)
Do changes in circadian rhythms promote aggressive behavior in people with Alzheimer’s?
Circadian rhythms are biological changes that occur over an approximately 24-hour cycle and include daily patterns of sleeping, eating and other processes. For people with Alzheimer’s disease, circadian rhythms become altered — promoting sleep disorders and behavioral problems associated with the disease. Individuals with Alzheimer’s often experience “sundowning syndrome,” which involves agitation and aggressiveness during the hours before sleep and may be closely related to circadian dysfunction. Sundowning syndrome can occur in as many as two-thirds of individuals with Alzheimer’s, and it plays a major role in determining whether these individuals are placed in long-term care facilities. Thus, there is a need to learn more about how circadian rhythms and behaviors are linked in dementia.
In initial studies in mice, William David Todd, Ph.D., and colleagues found that disruptions in a nerve cell circuit called the circadian timing system (CTS) increased aggression in normal mice during their inactive period, which corresponds to the evening hours when sundowning syndrome is observed in people with Alzheimer’s. The CTS is located in a brain region called the hypothalamus that helps regulate both circadian rhythms and behavioral aggression. For their current studies, the researchers will study how the aggressive behavior of Alzheimer’s-like mice changes as they age, and determine if this relates to the levels of beta-amyloid and tau in the hypothalamus. They will also study how altering activation of the CTS impacts the animals’ aggressive behavior.
Results of this effort could identify novel molecular mechanisms that link changes in circadian function to aggressive behaviors in Alzheimer’s disease. Importantly this work could inform the development of new therapies that target these changes to reduce behavioral problems and improve quality of life for individuals living with dementia and their caregivers.