Grant: CIHR Fellowship - Priority Announcement: Sex and Gender in Health Research

Alzheimer's is a progressive disease that affects many Canadians. It causes problems with memory and thinking due to the insufficient blood supply to the brain, which deprives the cells from oxygen and other important materials required for healthy brain function. The causes of this loss in blood supply to the brain during Alzheimer's disease are not clear. We will study the role of an interesting molecule present in the brain cells, known as metabotropic glutamate receptor 5 (mGluR5), in this reduction in blood supply to the brain. This molecule is important for proper brain function. However, during Alzheimer's disease, it can attach to another toxic molecule called tau, which is found in Alzheimer's brain and causes harmful effects on memory. We will isolate brain cells from mice and use them to study how tau binds to mGluR5 and affects its function in the brain. Additionally, we will use mice sick with Alzheimer's disease to study how this interaction between mGluR5 and tau causes the reduction in blood supply to the brain, and how it reflects on memory and animal behaviour. We will then test whether a drug acting on mGluR5 can increase this poor blood supply. Finally, considering that Alzheimer's disease affects more women than men and the reported differences in the available Alzheimer's disease treatments between sexes, we will also study the difference in mGluR5 function and its binding to tau between male and female mice. This research will provide a better understanding of the role of mGluR5 in Alzheimer's disease development and how it differs between males and females. It will also show if drugs acting on mGluR5 could be a promising treatment option for the management of the disease to be further tested in humans.