Summary

Our preliminary studies have discovered a role for a gene called PPAR-gamma in cognitive function in Alzheimer's disease. Since virtually nothing is known about PPAR-gamma regulation in the brain, the specific aims of this project are to define the PPAR-gamma signaling axis in brain regions that underlie the types of cognitive function that PPAR-gamma agonism improves.

Project Details

Recent clinical studies implicate insulin resistance as an important risk factor for Alzheimer's disease. A very successful diabetes treatment is PPAR-gamma agonism to increase insulin sensitivity. Unfortunately, this class of drug has serious side effects to peripheral organs including the heart. We have discovered that stimulating PPAR-gamma in the brain can reverse cognitive deficits in an Alzheimer's animal model that shows insulin resistance like humans with Alzheimer's. This project will lead to an understanding of how brain PPAR-gamma functions in learning and memory in Alzheimer's disease. This will lead to more selective (i.e., lacking peripheral side effects) cognitive-enhancing agents for Alzheimer's disease patients.