Grant: CIHR Fellowship

Alzheimer's disease (AD) affects more than 1.1 million people in Canada with a devastating emotional and physical burden. However, there is no effective cure or preventive therapy yet. In AD, it is believed that proteins called amyloid-beta (Ab) and tau progressively accumulate and spread throughout the brain leading to loss of brain cells and connections, and ultimately cognitive decline. As such, understanding and halting how Ab and tau build up and spread to different brain regions is key to discovering a new drug target and treatment strategy. Currently, several studies suggest that Ab and tau may spread through brain networks. Today, we can study brain networks and protein spreading using advanced brain imaging and statistical methods. However, existing methods rely on atlases (pre-defined regions) that fail to capture gradual and subtle changes in connectivity and pathology within and between neighbouring regions, limiting the identification of key areas driving disease progression. In this work, we will use a novel data-driven method to study smooth spatial changes in structural and functional networks and determine their link to pathology, genetics, and cognition. Our main objective is to study how brain connectivity affects the spread of Ab and tau proteins using two large cohorts. Then, we will test if different patterns of connectivity changes and protein spreading can be predicted over time. Finally, we will link gene expression in different brain regions with changes in connectivity to shed light on the underlying biological pathways that contribute to the abnormal spreading of proteins along brain connections. Understanding how brain connectivity, AD protein spreading, and gene expression are associated with each other will open up new perspectives on the development of new drug targets and personalized treatment strategies.