Grant: Banting Postdoctoral Fellowship Program

Alzheimer's disease (AD) is the most common cause of dementia, and unfortunately there are no effective treatments for this devastating disease. The Alzheimer Society of Canada estimates that without new treatments 1.4 million Canadians will be living with dementia by 2031. This will not only be tragic for all of the patients and their families affected, but the rapid increase in the number of patients requiring care is projected to overwhelm our healthcare system. A promising target for new treatments is correcting for changes in the body's internal time-keeping mechanism - the circadian system. Patients with AD often experience altered circadian rhythms, manifested as disrupted sleep. Importantly, recent findings suggest that circadian disruption is not only a consequence of AD, but precedes the memory loss and contributes to disease progression by increasing the accumulation of toxic amyloid-beta deposits in the brain. Because of this, targeting the circadian system with novel treatments could both prevent and slow the progression of AD. There are two types of synchrony in the circadian system that are important for good health. First, the body's internal timing must be aligned with the external environment. Negative experiences associated with jet lag and shift work demonstrate the effect that misalignment with the environment can have on health and well-being. Second, physiological functions in different regions of the brain and body must be coordinated in order for processes to occur at optimal times. This second type of synchrony, which is the focus of our research, has received much less attention even though it directly regulates critical cellular processes and may be a key factor in the progression of AD. Identifying and correcting maladaptive changes in the circadian system could improve the quality of life of patients and their families, reduce the economic burden of AD, and prevent the devastating memory loss associated with this disease.