The dementias associated with aging, including Alzheimer's disease, afflict a substantial segment of our aging society (5-15%), and place an extraordinary burden on the health care system. The cost of caring for patients with AD is estimated to be at least 25 billion. Despite the magnitude of this disorder, an understanding of the unique vulnerability of specific brain regions to the disease process is lacking. This pilot proposal seeks to contribute new data on the potential role of adrenal steroids in the observed vulnerability of neuronal populations in the hippocampus. The specific HYPOTHESIS we seek to test is: In AD there is an accelerated loss of glucocorticoid receptor containing neurons, and this neuronal loss will occur in hippocampal subfields which demonstrate the greatest vulnerability to the disease process. In order to arrive at examining this hypothesis, we will examine three specific aims. First, we will determine the distribution of glucocorticoid and mineralocorticoid receptor expression in human hippocampus. Second, we will determine whether aging alters the normal distribution or level of expression of these receptor subtypes. Third, we will determine if AD results in a specific loss of hippocampal neurons which contain the glucocorticoid receptor. These feasibility studies will provide, for the first time, information on corticosteroid receptors in the human brain and the effects of aging and AD on these receptors. Such data may provide new insights into mechanisms of neuronal vulnerability in AD.
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