Grant: Project Grant

Alzheimer's disease affects many Canadians, and it causes a decrease in memory with age. This reduction in memory is linked to insufficient supply of blood to the brain. Poor blood supply to the brain in Alzheimer's disease deprive cells of essential materials and leads to improper function but the causes of this short supply remain unclear. We will study how a molecule present in the cells of the brain called metabotropic glutamate receptor 5 (mGluR5) reduces the supply of blood to the brain and contributes to the development of Alzheimer's symptoms. We are interested in mGluR5 because it can attach to two toxic molecules commonly found in Alzheimer's brain called beta-amyloid and tau. Beta-amyloid and tau cause harmful effects on memory in Alzheimer's patients. Thus, we will first use brain cells isolated from mice to study how Beta-amyloid and tau binds to and alters the function of mGluR5. We will then use mice sick with Alzheimer's to understand how that attachment between beta-amyloid or tau and mGluR5 can lead to insufficient supply of blood to the brain and memory problems. Because Alzheimer's disease affects more women than men, we will also study if mGluR5 functions differently in male compared to female mice. Specifically, we will test if altering estrogen and testosterone function will affect how mGluR5 contribute to the poor blood supply to the brain in both sexes. Additionally, we will test if the drugs acting on mGluR5 can correct the poor blood supply to the brain and improve the symptoms of Alzheimer's in mice from both sexes. This research will help explain the major role that mGluR5 plays in the development of Alzheimer's disease and whether this role is different between males and females diagnosed with the disease. It will also show if drugs acting on mGluR5 should be tested in humans as a novel and promising treatment for Alzheimer's victims.