Project 464099

Discoveries spanning the last decade have provided essential insights into Alzheimer's disease by identifying, as an important risk factor, immune challenges that affect microglia, the brain's immune cells. Microglia were recently shown to be a diverse cell type (with many states co-existing in the brain), thus providing novel opportunities for selective targeting. Our research project aims to investigate microglial functional diversity in response to viral infection and Alzheimer's disease pathology, along the aging trajectory. We will focus on a microglial state named 'senescent' microglia, which are dysfunctional yet resistant to cell death, and could be specifically implicated in the onset of Alzheimer's disease. We will conduct state-of-the-art behavioural paradigms, imaging, as well as molecular analyses notably of senescent microglia using novel preclinical models. Treatment interventions normalizing these cells after viral infection will also be performed in these preclinical models. This research will bridge neuroscience and immunity to better understand, prevent, and treat dementia. By focusing on aging and the highly prevalent Alzheimer's disease, our results will provide an opportunity to develop therapeutic strategies that could change the lives of many afflicted or at-risk individuals in Canada, Israel, and globally.