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2007 Grant - Hebda-Bauer
How Overexpression of a Stress Gene Modifies Alzheimer's Disease Pathology
Elaine Karen Hebda-Bauer, Ph.D.
University of Michigan
Ann Arbor, Michigan
2007 Investigator-Initiated Research Grant
Elderly individuals exposed to high stress levels are more susceptible to development of Alzheimer's disease as compared with those not exposed to stress. Part of the explanation for this association is that stress increases levels of glucocorticoid hormones (such as cortisol), which are known to have detrimental effects on nerve cell function and survival. However, some individuals are more susceptible than others to the effects of stress, and genetic differences may account for some of the different responses to stress.
Elaine Hebda-Bauer, Ph.D., and colleagues have produced mice genetically altered to have increased expression of glucocorticoid receptors in the brain. They have found that the brains of these mice are more susceptible to stress, although the mechanisms responsible for such susceptibility are not well understood.
Dr. Hebda-Bauer and colleagues plan to continue their studies of how stress is related to the development of Alzheimer-like pathology. They plan to use their mice (which overexpress the glucocorticoid receptor) as well as mice genetically altered to develop Alzheimer-like pathology. By interbreeding these mice, they plan to study how the glucocorticoid receptor influences the age of onset of Alzheimer-like pathology, as well as its rate of onset. They will examine the brains of adult mice to study levels of beta-amyloid (a key characteristic of Alzheimer pathology) as well as levels of other factors related to stress.
These studies should improve our understanding of how stress influences the development of Alzheimer's disease, and how individual genetic differences affect this process.