Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Alzheimers Disease (AD) is the most common form of senile dementia, affecting approximately 500 000 people in Canada alone. It is a progressive neurodegenerative disease, causing loss of learning and memory, and eventually even the ability to sit upright, eat, or smile. Despite extensive research, causes of AD remain elusive. Recently, a theory has been proposed that neuron death in AD, and many other neurodegenerative diseases, is amplified by a loss of protection by microglia. Microglia are the immune cells of the central nervous system. They constantly survey the environment for infections and toxins, provide growth factors for neurons, and assist in tissue remodelling. However, like all replicating cells, microglia become less functional as they age and are then termed dystrophic microglia. Aging of other immune cells throughout the body can be regulated by how tightly their DNA is stored. Addition of chemical groups to the DNA-packaging proteins can either tighten or loosen the DNA, known as epigenetic regulation. There has been little research on epigenetic regulation in microglia. Therefore, I will determine if compounds that loosen DNA are capable of reverting aged microglia to a younger, more protective state, which can protect neurons from age-related damage. Firstly, cellular analyses will determine how DNA is packaged in young and aged microglia. I have access to healthy and AD tissue from both humans and rodents, which will help to clarify if dystrophic microglia appear before or after AD pathology, and if they develop in overlapping areas within the brain. I will also expose differences in young and aged microglial functions, and determine if altering DNA compaction can rescue dystrophic microglia and arrest learning impairment in rodent AD models. This research will contribute to knowledge on mechanisms of AD, and provide desperately-needed avenues for potential treatment and prevention of neurodegenerative disorders.