Chaperone-Mediated Protein Refolding Dysfuntion in Alzheimer's Disease

altered by AI' or to what degree it is altered in AD. We propose first to examine the effects of A~ on protein folding in primary neuronal and glial culture soluble extracts preparatory to evaluating rat brain and human brain extracts. Potential in vivo alterations in protein stabilization and folding induced by the presence of A~ will then be addressed in affected and unaffected brain regions in control mice and a transgenic model of A~ pathogenesis. Finally, alterations in protein stabilization and folding will be correlated with the progression of AD in control, MCI, early-, mid-, and late-AD affected and unaffected brain region extracts.