The Carbohydrate Connection: Finding a Way to Target Alzheimer’s

GlycoNet Investigator Dr. Matthew Macauley is uncovering how carbohydrates influence immune cells in the brain and their impact on Alzheimer’s disease.

 Posted: 8 January, 2024


Over half a million Canadians are living with Alzheimer’s disease or another form of dementia1 and that number continues to increase. This underscores the need for research aimed at unravelling the complexity of the disease and developing novel therapies. One promising area of science is the growing field of glycomics—the study of elemental carbohydrates known as glycans, which play vital roles in many biological processes.  


GlycoNet investigator Dr. Matthew Macauley is one of the researchers leading the way in applying glycomics to uncover the mechanisms of Alzheimer’s disease. Dr. Macauley is an Associate Professor and the R.U. Lemieux Chair of Carbohydrate Chemistry at the University of Alberta. His lab is studying how carbohydrates influence the function of immune cells in the brain called microglia. Understanding how these microglia impact the progression of Alzheimer’s disease provides opportunities to explore new therapeutic pathways. 


In particular, Dr. Macauley and his team have been investigating two forms of a carbohydrate-binding receptor, called CD33, and the opposing effects of these two versions on microglia. They found that one version acts as a brake inhibiting the function of these microglia, while another shorter version acts as an accelerator, boosting the microglia’s ability to prevent the buildup of neurodegenerative “plaques” and maintain healthy function. 


“About 10% of people make more of this shorter form and they have less of a chance of getting Alzheimer’s disease,” said Dr. Macauley.


The research team is working to understand why that’s the case, with the goal of leveraging that knowledge towards developing a therapeutic treatment for Alzheimer’s disease.


 “The fundamental nature of our findings is fine-tuning how we think about the best therapeutic modality to target CD33.” 


Dr. Macauley’s research fits within the emerging field of glycomics, an area of science full of untapped potential. Part of the challenge of answering research questions in glycomics is the need for better tools and methods to study carbohydrates in biological systems. As a result, developing tools is one of the focuses of Dr. Macauley’s lab as they work towards understanding the biological roles of carbohydrates and translating that knowledge into therapeutic applications.


“Just as proteomics and genomics really accelerated decades ago, once the technologies for studying carbohydrates are sufficiently developed to allow now-carbohydrate experts to easily enter the field, the area of glycomics will likewise explode,” said Dr. Macauley.


Dr. Macauley’s research accomplishments and scholarly activity have been recognized by several prestigious awards. He most recently received the 2023 Glycobiology Significant Achievement Award, presented by Oxford University Press at the Society for Glycobiology Annual Meeting held in November. The award recognizes a mid-career scientist who has made key discoveries with the potential for significant impact in glycoscience. Dr. Macauley was also one of two recipients of the 2023 Killam Accelerator Award at the University of Alberta, which includes a funding prize of $75,000 per year for three years. 


“I’d like to give my team a lot of recognition for these awards,” Dr. Macauley added, noting that those in his lab are the ones doing the experiments while he enjoys mentoring graduate students, postdocs, and undergraduates. 


As a proud mentor, he’s now seeing the first set of PhD students from his lab defend their theses. Recent PhD graduates are obtaining exciting postdoc positions at internationally recognized labs in Canada and abroad. 


Dr. Macauley hopes he’s inspiring the next generation to continue in science. For those considering a path in the glycosciences, he shares some words of encouragement: “My advice would be to stick with it. It’s not always a straight path—in glycoscience, you don’t necessarily have all the tools at your disposal like other mainstream fields of research. I would encourage young scientists to be thinking of ways to innovate and develop because there’s still a lot of room for innovation.” 


“It’s an exciting time with a lot of new technologies and advancements coming on board in the area of glycomics.”

1Alzheimer Society of Canada

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