Grant: Operating Grant

------------------------------------------------------------------------- 17% of Canadians have someone with Alzheimer disease (AD) in their immediate family. It is thus imperative to identify new drug targets to help the patients and their caregivers. PAK (p21-activated kinase) is an enzyme in the brain. Defects in PAK have been associated with mental retardation. Our hypothesis is that PAK progressively becomes defective in AD as well. This hypothesis is first based on observations made in the brain of patients who died with AD. For example, we found that the more severe were the clinical symptoms of AD, the greater was the decrease of PAK. We then discovered that a decrease of PAK was also present in an animal model of AD. We are thus proposing here to investigate the role of PAK in this animal model using various strategies. Will inactivating PAK make the animals sicker? Conversely, will stimulating PAK be beneficial for the mice? For example, we will use omega-3 fatty acids as one of the strategy to boost PAK activity in the brain. If we succeed in confirming that PAK plays a key role in our AD model, we could then develop drugs that target PAK. In summary, we hope to decipher a molecular mechanism in the brain that could lead to the development of new treatments for AD.