Understanding Genetic Variants in Alzheimer’s Disease

What biomedical issue did you address in your research and what did your studies find?

My Ph.D. research focused on genetic variants and their effects on Alzheimer's disease (AD), including brain blood vessel function and the progression of molecular changes. I explored how the gene variants known as APOE ε2 and APOE ε3 affect inflammation, blood flow changes and the buildup of toxic proteins in the brain, which are key factors in cognitive decline during aging and AD.

I used a combination of approaches, looking at biomarkers that exist in human cerebrospinal fluid and also studying mouse models with APOE variants selectively expressed in blood vessel cells. In samples of cerebrospinal fluid from patients who had previously consented to be part of a study, we identified a protein called REG4 linked to worsening memory and AD progression, along with inflammation-related markers that could help detect the disease early. In mouse models, we found that APOE ε2 is generally protective; while it creates vulnerabilities in specific blood vessel types, it also improves the clearance of harmful proteins. Our findings help explain why some individuals are more resilient to AD. This research connects genetics, brain health and aging, and provides potential pathways to develop targeted therapies that may prevent AD.

What aspects of Mayo's culture helped you grow as a scientist and as a thinker?

I completed the Clinical Innovation and Entrepreneurship Program through the Mayo Clinic Office of Entrepreneurship. The program was a yearlong training course to test, validate, and pitch a transformative healthcare innovation idea, taking it from problem to solution to pitches for funding. I worked on an entrepreneurial project that used artificial intelligence to organize patients' X-rays and other imaging tests, and I learned product development and business skills. Through this experience, I secured an exciting internship in industry. I also joined the Yale University-Mayo Clinic Center For Excellence in Regulatory Science Innovation program, where I gained in-depth insight into the inner workings of the Food and Drug Administration. Through this program, I received funding to present my work at an international conference in South Korea and was subsequently recruited to the next stage of my career training.

In addition, I participated in Mayo's Initiative for Maximizing Student Development (IMSD) program, which provided invaluable resources for my growth as a scientist and, more importantly, fostered a strong sense of community. Through IMSD and the support I received, I was able to "pay it forward" and become a mentor for undergraduate and new Ph.D. students. I am grateful for the opportunity to mentor students and support graduate school recruitment efforts.

What's next?

My Ph.D. training has been invaluable in preparing me for the next steps in my career. I'm excited to build on this foundation as I begin a fellowship in clinical chemistry at the University of Pennsylvania.