Grant: Doctoral: Vanier Canada Graduate Scholarships

The human brain contains nearly 700km of blood vessels, so it is no surprise that brain health and vascular health are closely related. One of the biggest threats to brain health as we age is Alzheimer disease, a type of dementia that currently affects over half a million Canadians. The main genetic risk factor for Alzheimer disease is a version of a gene called "APOE", which makes a protein that acts as the FedEx of the body - transporting fats and other proteins in the brain and through the blood vessels. Most work trying to figure out how APOE connects to Alzheimer disease has looked at how it works in the brain, largely overlooking what it does in the blood vessels. One way that the APOE protein transports its cargo through the blood vessels is by sticking to high-density lipoproteins (HDL) - commonly known as the "good cholesterol". HDL supports blood vessels in many ways, and the proteins stuck to the particles dictate their function. HDL carrying the APOE protein has been shown to have extra protective functions in the context of heart disease but has not yet been studied in the context of Alzheimer disease and dementia. This project will take a new approach to understand how APOE and Alzheimer disease are connected by looking outside of the brain, and focusing on HDL carrying the APOE protein in the blood. The first goal is to discover exactly how these particles protect brain-specific blood vessels, and this will be done by modeling vessels using human cells in a dish and treating them with HDL from human blood. It will also explore whether the amount of the particles in someone's blood can help diagnose or predict their risk of developing Alzheimer disease, by measuring the particles in blood banked from a nation-wide aging study. This research could lead to prevention and treatment avenues for Alzheimer disease that wouldn't need to enter the brain to be effective, and advance the international search for an Alzheimer disease blood test.