Grant: Project Grant

In Canada, ~17 millions of adults between 30-64 y old could benefit from a prevention strategy to lower the risk of Alzheimer's disease (AD). Although a lot of epidemiological studies reported positive cognitive outcomes in populations eating fish, there is skepticism about the link between docosahexaenoic acid (DHA), an omega-3 (OM3) fatty acid in fish and prevention of cognitive decline. This is largely because there is a disconnect between epidemiological, molecular and animal studies which generally favor a link between higher DHA intake and cognition whereas clinical DHA and fish oil trial data are less consistant. There are several knowledge gaps in this field that might explain why clinical trials were not successful but this proposal will focus on two major gaps: OM3 fatty acid metabolism and the blood-to-brain DHA link. OM3 supplements in cardiovascular disease have faced the same issues for decades but the more recent trials have now generated the clinical evidence supporting primary and secondary cardiovascular events reduction and a better risk to benefit balance of OM3 drugs compared to statins, for instance. What if, for cognitive decline, we just have missed the target because the supplement/drug formulations were not appropriately designed to target the brain? We hypothesize that (i) E4 carriers display a faulty packaging of circulating OM3, leading to reduced available OM3 for brain cells, (ii) The use of new OM3 formulation can direct plasma OM3 into brain compartments more readily available for the brain, thereby increasing brain OM3 concentrations and improving cognition. We will perform studies in mice and humans to test OM3 metabolism and the blood-to-brain OM3 link. Ultimately the information generated in this grant application will help to better design clinical trials in terms of fatty acid formulation, expected level to reach in the plasma and the brain.