Grant: Master's Award: Canada Graduate Scholarships

A Possible Association Between Insulin and Alzheimer?s Disease: Examining the Consequences of Altered Insulin Signalling on the Expression of Human Amyloid-Beta in Caenorhabditis elegans

"Alzheimer's Disease (AD) is a neurodegenerative disease that affects millions of people globally. This disease of ageing has been associated with amyloid-beta and tau plaques in the brain, causing symptoms such as confusion, memory loss, and impaired cognitive abilities. It is known that insulin is a key regulator in the ageing process, as well as other processes such as metabolism and fat storage. An association between insulin regulation and amyloid-beta plaque accumulation has been noted in <em>C. elegans</em>. This study uses <em>C. elegans</em> to compare how different mutations in the insulin signalling pathway affect the deposition of human amyloid-beta in a transgenic worm strain over-expressing human amyloid-beta peptide. Previous work in our lab has showed reduced function of the insulin receptor can rescue worms from amyloid-beta induced toxicity in behavioural assays. We now want to study how insulin regulation could affect amyloid-beta toxicity by investigating antagonistic insulin molecules. Worms which over express antagonistic insulin will be tested to see if they can counter the effects of over expression of human amyloid-beta peptide. Chemotaxis behaviour and time to paralyze will be monitored. Additionally, in-situ antibody staining and western blots will be completed to detect the amount of protein present in the worms. Our lab has engineered an insulin molecule which is originally an agonist but is showing antagonistic properties with the alteration of certain amino acids in its coding sequence. This study aims to confirm if this engineered insulin-like peptide acts antagonistically in the AD model. These findings are important for determining how insulin signalling is able to alter to progression of amyloid-beta deposits and determining future therapeutics for AD."