Some older adults have brains full of amyloid plaques, the sticky protein deposits linked to Alzheimer’s disease, yet they never develop dementia. Despite having the same buildup found in Alzheimer’s patients, their minds stay sharp. Understanding the reason for this resilience could unlock the first breakthrough treatments in decades.
Dr. Stefan Wendt came to UBC to help solve that mystery. After finishing his graduate studies in Berlin, he was drawn to the work of Dr. Brian MacVicar, Professor in the UBC Department of Psychiatry and Canada Research Chair in Neuroscience. Both scientists wanted to study how the brain’s immune cells, called microglia, respond to damage caused by Alzheimer’s disease.
With remarkable foresight, the McArthur, Aune and Copland families recognized a unique opportunity for philanthropy to catalyze innovation in Alzheimer’s research at UBC. The friends’ gift in 2021 enabled Dr. MacVicar to team up with Dr. Haakon Nygaard, Fipke Professor in Alzheimer’s Research at UBC and Director of the UBC Hospital Clinic for Alzheimer Disease and Related Disorders, to develop miniature brain models, called neurospheres, that allow scientists to study Alzheimer’s in the lab, potentially accelerating the search for treatments.
The gift also enabled Dr. Wendt, a postdoctoral fellow, to join this interdisciplinary collaboration. The human brain models they created marked a transformative breakthrough, sparking new confidence in the potential to discover, develop and test a disease-modifying treatment for Alzheimer’s at UBC.
With further donor support, the team expanded this vision and engaged Dr. Freda Miller, Professor in the UBC Department of Medical Genetics, Michael Smith Laboratories and the School of Biomedical Engineering, who brings expertise in mapping which genes are active in brain tissue. Dr. Wendt is now refining the process to grow thousands of these mini-brains simultaneously, building a drug testing platform at UBC to identify therapies that could slow or prevent Alzheimer’s disease.
For 30 years, new drugs for Alzheimer’s have been scarce. If this UBC team can identify what protects resilient brains, those mechanisms could be replicated in therapies for patients.
“Given how few advancements were made over the decades in new drugs for Alzheimer’s disease, this would be absolutely groundbreaking for families and patients.”
Dr. Stefan Wendt
A protective mystery
This research brings together UBC’s experts in neuroscience, data science and genetics in a true team science effort to find the molecules that protect some brains from Alzheimer’s. By combining UBC’s strengths in cell biology, imaging, genetic analysis and computer modeling, together with state-of-the-art lab spaces, the team is building a complete picture of why some brains stay healthy longer than others.
For reasons researchers do not yet understand, the usual progression from plaques to dementia is prevented or dramatically slowed in certain individuals. Uncovering this mystery and learning how to protect other patients’ brains is a central focus of their work.
Dr. Wendt helped launch the research, which was catalyzed by donor support, shaping its goals and direction. While he refines the brain model production process, other partners analyze resilient brain tissue. The work happens in parallel, coordinated toward identifying therapies that could protect patients from Alzheimer’s.
“We believe that, once we find new genes and proteins that could explain Alzheimer’s disease resilience, we will need a testing system to understand how they work before developing new therapies,” says Dr. Wendt.
Seeing genes in action
The past year brought breakthroughs that energized the team. They published their brain model in early 2025 in the Journal of Neuroinflammation. Soon after, a collaboration with the Miller lab enabled a new approach to map which genes are active in specific areas of the brain and reveal what protects some brains from Alzheimer’s damage.
“This got us all very excited, because we will be able to use the same technique to look at where genes are active around amyloid deposits in actual resilient brain tissue,” he says. This work could reveal how specific cells protect themselves from damage and point to new treatment targets.
The team established a collaboration with Dr. Anna Fracassi at the University of Texas, who provides brain tissue from resilient patients. They also work with Dr. Xin Tang, a new UBC faculty member at Michael Smith Laboratories, on the computer analysis required for the complex genetic data.
Building blocks of discovery
The 2021 gift from the McArthur, Aune and Copland families funded research that inspired a bold vision to accelerate the discovery of therapeutics for Alzheimer’s disease here in British Columbia. By uniting world-class scientists and clinicians with donor support, UBC is building capacity to deliver breakthrough treatments developed and tested in our own communities, with the people of this province among the first to benefit from these discoveries.
This collaborative model is already working. It brought together Dr. MacVicar’s expertise in neuroscience and advanced imaging with Dr. Nygaard’s clinical knowledge of Alzheimer’s disease, enabling them to explore shared questions from different perspectives. The Djavad Mowafaghian Centre for Brain Health provided the physical home and clinical-academic community for this work, and philanthropy allowed the team to recruit emerging talent like Dr. Wendt, expanding research capacity, mentoring early-career researchers and driving innovation.
Today, Dr. Wendt works closely with undergraduate student Ada Lin on experiments and data analysis, while graduate students Jane Da Young Kong and Sarah Ebert handle genetic analysis. The team frequently runs results by Drs. Nygaard, MacVicar and Miller, planning next steps together. This collaborative structure, which brings together students, postdoctoral fellows and principal investigators, was made possible by philanthropic support that gives the team stability and time to advance their research without constantly seeking grant funding.
“The financial security allowed me to stay focused on our tasks, which has been wonderful,” says Dr. Wendt. “The tools and technologies we use are incredibly costly. The support helped us focus on finding the absolute best solutions.”
Genetic analysis tools moved the work forward. Donor support gave the team confidence to commit without hesitation, and the Miller lab has now acquired equipment to perform these experiments in-house at UBC, accelerating the research.
Two years to discovery
The team expects to identify promising therapeutic targets within two years. Dr. Wendt is finalizing the upgraded brain model system and continuing the genetic mapping analysis. The acquisition and analysis of human brain tissue from resilient patients will be another major focus.
If more support becomes available, the team plans to invest in automated microscopes and handling equipment to scale their drug testing system, potentially accelerating the path to treatments.
“I cannot emphasize enough how much donors helped us,” he reflects. “We could absolutely not do this without their support. I believe we are well on track to achieve our goals.”
To learn more about supporting Alzheimer’s research at UBC, please contact Erin Bartlett at erin.bartlett@ubc.ca.