Grant: China-Canada Joint Health Research Initiative

Our understanding of the progression of Alzheimer Disease at the molecular level remains limited. In recent year, we have realized that specific changes are occurring in lipids that must be reflected at the protein level. We hypothesize that the study of the global protein changes that occur in very specific regions of the brain will provide a better understanding of the processes involved AD. Ultimately, this would provide new targeting strategies to prevent cognitive decline in vivo. We propose to use global studies of the changes that occur in protein levels(Proteomics) in animal models of Alzheimer Disease in comparison to the corresponding wild-type model. We also propose to study the global changes in a protein modification associated with signalling (phosphorylation). The global measurements of protein levels and protein phosphorylation levels in combination with pathway/network models and our expertise in neuroscience will be used to discover specific group of proteins and their phosphorylations that are changing during the disease and might represent novel targets to affect lipid metabolisms. The potential targets will then be validated using conventional biochemistry and neuroscience methods. The outcome of this project will be better understanding of the processes involved in AD and novel validated targets for the modulation of metabolic pathways.