GlycoNet investigator Matthew Macauley awarded major grant from the Canadian Institutes of Health Research

By Marie-Christine Houle

As Canadian Alzheimer’s Awareness Month wraps up, we shed some light on the work of Matthew Macauley, a GlycoNet investigator and professor in the Department of Chemistry at the University of Alberta. He was recently awarded a major five-year grant from the Canadian Institutes of Health Research (CIHR), worth $749,700. This project builds upon work previously funded by GlycoNet.

The project aims to clarify the role of CD33, a protein on white blood cells in the brain called microglia, which bind sugars.

“To use a very simple metaphor, microglia are like the janitorial staff of the brain. Among the many important things they do, they help prevent accumulation of unwanted material, such as proteins. They play a role in pathogenesis of Alzheimer’s disease. Accumulation of amyloid-beta, in particular, can lead to the formation of neurodegenerative plaques in the brain. This is one of the reasons microglia are increasingly being viewed as important in preventing this accumulation under healthy conditions” says Macauley.

Studies have shown that two different versions of CD33 are found in the human population. In previous studies, individuals who have a version of CD33 that does not bind its sugars was shown to be highly correlative with protection from Alzheimer’s disease.

Using a mouse model, Macauley and his team are looking at the cause-effect relationship between the different versions of CD33 and microglia’s ability to dispose of cellular debris. Macauley explains that once these proteins aggregate, there appears to be no turning back. This type of plaque (aggregated proteins) has been found in all people who develop Alzheimer’s disease. This key trigger eventually leads to the devastating loss of brain function.

“Current studies point to the need to prevent the accumulation of plaques in the first place. That is why it is so important we understand how CD33 regulates the process of plaque accumulation,” he adds.The Alzheimer Society of Canada reports that 747,000 Canadians are living with Alzheimer’s or another dementia. By 2031, that number it is estimated that 1.4 million Canadians will suffer from Alzheimer’s or another dementia. Women are disproportionately affected, representing 72% of cases.

Macauley, who trained as an immunologist during his postdoctoral studies, believes that his laboratories interdisciplinary approach to research provides a unique opportunity to tackle an issue that is central to human health. His ultimate goal is to perform research that will impact people’s lives. He hopes his research will lead to tangible benefits for people at home and worldwide.