When cultured with senile plaques obtained at autopsy from individuals with AD, microglia release a potent neurotoxic factor. The present proposal is designed to identify the stimulus for the production of this microglial factor by determining the specific sequence(s) within the beta-amyloid peptide responsible for microglial attachment and activation of neurotoxic activity. Preliminary data is presented demonstrating that, in vitro, microglia adhere to beta-amyloid and are stimulated to initiate an immunologic cascade which results in neuronal injury. A number of approaches to interrupt this cascade and prevent the production of this neurotoxin are proposed, with the long-term goal of preventing neural loss in AD.
