As many as 5.5 million Americans over the age of 65 may have Alzheimer’s disease, a progressive brain disorder that currently has no cure, according to the National Institutes of Health.

Fourth-year Virginia Tech Carilion School of Medicine student Christopher Liao, focused his research project at the school on the disease, looking for how it may impact blood vessels in the brain, specifically in early stages of the disease. He carried out his research project under the mentorship of Ian Kimbrough, assistant professor in the School of Neuroscience in the College of Science.

“The pathogenesis of Alzheimer’s disease is not well understood, but one hypothesis is that it may be related to the build-up of plaques around the blood vessels in the brain,” Liao said. “Previous research has shown that these plaques originate from amyloid-beta, which is a natural protein created by the body, but if it accumulates to excessive levels, it can clump together and wrap around blood vessels to create a rigid cast.”

Kimbrough published a 2015 paper in the journal Brain that showed this amyloid cast prevents blood vessels from fully dilating and constricting, preventing neurons in the brain from getting the nutrients they need to perform optimally. Neurons transmit messages from different parts of the brain and from the brain to other parts of the body.

“It is like a runner running out of fuel. They need energy to perform. Neurons have to have enough fuel to process information to do a range of things like process visual information and sound and recall memories,” Kimbrough said.

They also found that the amyloid proteins get in between blood vessels and specialized supporter cells, called astrocytes, that help communicate between vessels and neurons. That finding prompted Liao’s project with the goal to determine whether there was an initial event causing the astrocytes to detach from the blood vessel wall, disrupting communication even before plaques develop.

“In order to prevent Alzheimer's disease from happening, you ideally want to be able to intervene at an earlier stage. The optimal solution would be to catch it before it becomes a disease and presents itself clinically,” Liao said. “That was the thought process behind why we wanted to understand this disease process from an earlier time point.”

Liao used an earlier, premature form of amyloid called oligomers to try to see what happened to the blood vessels and astrocytes before any plaques formed, using a mouse model. They found the amyloid-beta oligomers caused overexpression of astrocytes and other supporter cells, called microglia. The data suggested that these cells reacted to the foreign substance by releasing collagen-degrading enzymes to clear the amyloid, but doing so also negatively impacted the structural integrity that holds the astrocyte onto the vessel. This degradation can impact the astrocytes’ ability to regulate blood flow and maintain the blood-brain barrier, and may create an empty space for the amyloid-beta to occupy and form plaques around the vessels, further reducing blood flow to neurons.

The findings are a potentially valuable step for future research to build on with the hope to intervene earlier to help prevent or slow the progression of Alzheimer’s disease.

While Liao will do plastic surgery residency in Long Island, New York, at the Nassau University Medical Center and Stony Brook University Hospital after he graduates, he was drawn to this project because it was translational, and the work he was doing in the lab was easy to envision impacting future patients. “That's what really inspired me and motivated me to continue with this project. I just wanted to discover a unique way to block this debilitating process from happening in the first place,” Liao said.

“For me, mentorship with Chris has been very much a joy because he's an exceptional scientist and a hard worker. His work ethic is among the top of anyone that I've worked with,” Kimbrough said. “Even with all of his other medical school obligations, the amount of time Chris put in the lab was extraordinary, and he took ownership of the project.”

Liao was drawn to the Virginia Tech Carilion School of Medicine in part because of its research-intensive program. He did research during and after his undergraduate education and plans to continue contributing to the research community as a physician. “You have to be curious enough to ask important questions like how and why things are happening, why things are the way they are, and what you can do to improve the world,” Liao said. “Research has really shaped me and helped refine my perspective on discovery and innovation.”

Liao is one of eight students in the class of 2020 who received Letters of Distinction for their research project. Each will deliver an oral presentation at the 2020 VTCSOM Medical Student Research Symposium on March 27. The symposium will be virtual with a live stream of the oral presentations available.