Grant: Doctoral: Vanier Canada Graduate Scholarships

Dr. Annie Vogel Ciernia & Dr. Brian MacVicar, University of British Columbia. Sporadic or late-onset Alzheimer's disease (AD) is a serious health concern, impacting nearly 10% of people over the age of 65 worldwide. The largest genetic risk factor for AD is the possession of at least one e4 copy of the Apolipoprotein E (APOE) gene. APOEe4 has previously been shown to result in changes in brain cell metabolism and lead to increased inflammation in the brain and subsequent neurodegeneration. Microglia are the resident immune cells of the brain and are the main executors of brain inflammation. In a healthy brain, microglia establish a protective memory state after one immune challenge which prevents them from inducing inflammation upon subsequent immune challenge. However, my preliminary data suggests that mouse microglia that have the humanized APOEe4 gene cannot establish the protective memory state leading to excessive inflammation. My research proposal aims to understand how possession of the APOEe4 gene changes microglial immune response and memory. For this, I will study how microglia respond to immune challenge both in healthy and APOEe4 mice. I will examine the cellular biology looking specifically at mechanisms that control inflammation including cellular metabolism and gene expression control. As a result, the proposed research will uncover the role of microglia in sporadic AD and contribute to the understanding of how APOEe4 increases risk for AD development. The research will investigate the establishment of the microglial memory state which can identify possible future therapeutic targets for sporadic AD.