Grant: Project Grant

Alzheimer's disease and diabetes mellitus, two of the most serious public health concerns of our times share many commonalities. In Alzheimer's disease, abnormal deposition of the amyloid protein in the brain is linked to destruction and death of brain cells involved in learning and memory. In a similar manner, the presence of another protein, human amylin, discovered in the pancreas of diabetic patients, renders insulin-producing cells dysfunctional. Work from our laboratory has shown that both amyloid and amylin exert their damaging effects on cells through the same receptor or "keyhole". We have therefore been working with compounds, which block the amylin receptor/keyhole in the brain, and thus can protect brain cells from toxic effects of amyloid. More recently, we have used such amylin receptor blocking drugs to improve the memory and learning deficits in mice, that have been genetically engineered to develop Alzheimer's disease. In this project, we plan to #1) genetically deplete the amylin receptor (keyhole) in Alzheimer mice thus preventing the amyloid in the brains of these animals from damaging brain cells, and in the process delay or prevent the development of Alzheimer-like symptoms, #2) develop drugs that can be easily penetrate the brains of Alzheimer's mice, block the amylin receptor/keyhole and thus alleviate the memory problems. At present there is no treatment for Alzheimer's disease other than for its symptoms. Studies such as those contained in this proposal may identify newer therapies based on protecting nerve cells from the deleterious effects of amyloid-beta in the brains of AD patients and thus slowing or preventing the disease altogether.