Project Overview

Alzheimer’s disease (AD) affects nearly one million Canadians and remains without a cure. Although most research has focused on the build-up of abnormal proteins such as amyloid and tau, we now know that inflammation in the brain’s immune system plays a major role in how the disease starts and progresses. What remains unknown is where in the brain these immune reactions begin and how they relate to the toxic proteins that spread through the brain. This project aims to map inflammation across different brain regions from people who donated their
brains for research after living with Alzheimer’s disease. We will study both young-onset AD (symptoms before age 65) and late-onset AD, since younger patients often have a faster disease course that may be driven by different immune responses. Using advanced laboratory methods, our team will measure thousands of inflammatory proteins and detect very small amounts of abnormal tau, amyloid, and other proteins such as α-synuclein and TDP-43—both also linked to Parkinson’s and other brain disorders. By combining these results, we will create the first regional “map” of inflammation in Alzheimer’s brains.

Next, we will use cutting-edge imaging mass cytometry, a technology that allows dozens of cell types and immune signals to be visualized in a single tissue section. This will show precisely which immune cells—such as microglia and astrocytes—are active around abnormal proteins and how they interact. Together, these studies will reveal how inflammation and toxic proteins influence one another, and why these processes differ between younger and older patients. The results will help guide future treatments that target the brain’s immune system and improve the development of early-detection tests in blood or spinal fluid.

Principal Investigator

Carmela Tartaglia , University Health Network

Team Members

Gabor Kovacs, University Health Network

Jennifer Gommerman, University of Toronto

Ivan Martinez-Valbuena, University Health Network

Joan Wither, University Health Network

Mohit Kapoor, University Health Network

Valeria Ramaglia, University Health Network

Partners and Donors

Krembil Foundation