An NIA funded K01 Mentored Research Scientist Development Award will provide valuable training in the fields of aging and Alzheimer?s disease to facilitate my career as an independent research investigator. This grant mechanism will not only allow for critical scientific training, but also valuable career development under the mentorship of Dr. David Holtzman. During this award period, I propose to investigate the association between cognitive function and circadian rhythms during the aging process and Alzheimer?s disease (AD) progression. Cognitive decline is associated with aging and is the defining feature of AD. Circadian rhythms, which are 24-hour oscillations in behavior and physiological functions decline with age and are severely blunted with AD progression. In fact, recent studies suggest disruptions to the circadian system may occur prior to the clinical onset of memory deficits in AD. Yet, mechanisms by which the circadian system impacts cognitive processes during aging and AD pathogenesis are relatively unknown. The goal of this project is to test the hypothesis that the decay in circadian rhythmicity as observed in aging and to a greater extent in AD, causes pathological disturbances in brain regions associated with memory processing. The following aims will test this hypothesis: (1) Examine the circadian oscillation of transcriptional, biochemical, and electrophysiological processes in brain regions which support memory function in mouse models of aging and AD. (2) Examine the effects of altering circadian function on behavioral, physiological, and molecular rhythms, and if this intervention influences AD pathogenesis. The concepts and methods in this proposal are innovative and have the potential for substantially impacting our understanding for the role of circadian function on memory in aging and AD progression. Our long-term goal is to identify possible strategies to ameliorate cognitive impairments and disease progression.
Cognitive decline is associated with aging and is the defining feature of Alzheimer?s disease. There is no effective treatment to slow Alzheimer?s disease progression. This project has the potential to identify new treatments by studying the relationship between the circadian system and cognitive function during the aging process and Alzheimer?s disease progression.
|Kress, Geraldine J; Liao, Fan; Dimitry, Julie et al. (2018) Regulation of amyloid-? dynamics and pathology by the circadian clock. J Exp Med 215:1059-1068|