ROLE OF GLUTAMATE IN ALZHEIMER'S DISEASE

$0P30FY2002AGNIH

University Of Texas Sw Med Ctr/Dallas, Dallas TX

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Abstract

Alzheimer's disease is characterized by deficits in learning and memory. Hippocampal NMDA and non-NMDA (kianate and quisqualate) glutamate receptors have been implicated in the acquisition and storage of memory. Interestingly, both NMDA and quisqualate hippocampal receptors are significantly reduced in Alzheimer's disease patients. This suggests that glutamate dysfunction may be an important component in the expression of Alzheimer's disease symptomatology. We hypothesize that quisqualate mediated phospholipase C activity is decreased in Alzheimer's disease and that this results in impaired cellular function. To test this hypothesis, quisqualate stimulated IP3, protein kinase C activity and distribution ill be examined in Alzheimer's patients and non-Alzheimer's control patients. These studies will determine whether the loss of hippocampal glutamate receptors observed in Alzheimer's disease can be functionally correlated with a loss of glutamate induced neuronal activation.

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