Graduate students at the University of Arizona Health Sciences Center for Innovation in Brain Science are pioneering research aimed at uncovering new pathways to combat Alzheimer’s disease. By examining neuroinflammation and leveraging data science to identify genetic risk factors, the researchers are advancing precision medicine approaches that may one day help to transform Alzheimer’s diagnosis and treatment.
This work, rooted in a commitment to diverse perspectives and community-focused solutions, is funded by a National Institutes of Health grant, “Translational Research in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias,” or AZ-TRADD. Co-led by Roberta Diaz Brinton, PhD, and Kathleen Rodgers, PhD, the program seeks to develop new strategies for earlier interventions and more personalized care for those at risk of Alzheimer’s.
Advancing Alzheimer’s research and taking knowledge home
Growing up on the Navajo Nation, Angel-Grace Charity Leslie’s life revolved around family. She took after her grandmother’s love of nature and shared a special bond with her oldest brother.
Sadly, her brother developed epilepsy while Leslie was in elementary school. “I was with him the first time he had a seizure. That’s when we started going to doctor’s appointments and neurology exams,” she said. “He was very sick while I was growing up and suddenly passed away in 2020. I wanted to help him and people like him. That’s what got me here.”
“Here” is the U of A Health Sciences, where Leslie, a medical pharmacology doctoral candidate at the U of A College of Medicine – Tucson, is part of a unique training program at the Center for Innovation in Brain Science. Her drive to understand the brain’s connection to epilepsy led her to Rodgers, the center’s associate director of translational neuroscience and a professor of pharmacology at the College of Medicine – Tucson.
Leslie first visited the U of A in 2019, as an undergraduate at Diné College, where she participated in the Undergraduate Readying for Burgeoning Research for American Indian Neuroscientists, or URBRAIN program. Funded by a $1.3 million NIH grant, URBRAIN encourages Native American students to pursue neuroscience and advance to top research universities, like U of A.
“URBRAIN is really where I got my start with data science,” Leslie said. “It made my work now as a graduate student possible.”
In a healthy brain, billions of neurons transmit information through electrical and chemical signals. When these neurons stop working together, as in Alzheimer’s, it leads to cognitive decline. Amyloid plaques, a hallmark of Alzheimer’s, disrupt neuron communication. Normally, immune cells clear these plaques, but in Alzheimer’s, they accumulate between neurons, causing chronic inflammation and damaging brain cells.
Leslie is studying the immune system’s response to amyloid plaques in mouse models of Alzheimer’s. Her goal is to track inflammation over time and use it as a potential marker for disease progression.
For Leslie, these programs are not just steppingstones to a career but a path to help her community. “Back home we have a saying: ‘Go into the world, learn as much as you can, and bring it back,’” she said. “Knowing that I might bring this critical knowledge back to the Navajo Nation gives me a lot of pride.”
Alzheimer’s disease is the seventh leading cause of death in the U.S. and the most common cause of dementia among older adults. Native Americans are at higher risk of developing Alzheimer’s or other forms of dementia than other groups.
Solving Alzheimer’s precision medicine questions with data
Coco Tirambulo’s journey into the complexities of neurodegenerative diseases was not borne solely in a lab. It stemmed from a childhood surrounded by the love, empathy and the realities of aging.
Her parents, who immigrated from the Philippines, operated assisted living care homes in Tucson, where Tirambulo witnessed firsthand the effects of dementia, Alzheimer’s, and other age-related conditions.
“It was a very nurturing environment, like having many grandparents, aunts, and uncles around,” said Tirambulo. “When I was growing up there, I had no idea that a lot of them had chronic illnesses. But as I grew older, that’s what led me to go into the health sciences because, as a Filipino American, we have the mindset that we care for elders as they grow older.”
After high school, Tirambulo attended Brandeis University in Massachusetts, where she earned a Bachelor of Science in Biology. Back in Tucson, she earned two master’s degrees: one in epidemiology from the U of A Mel and Enid Zuckerman College of Public Health and another in cellular and molecular biology as part of the Pre-Medical Admissions Pathway at the U of A College of Medicine – Tucson.
Tirambulo’s desire to help those at risk for Alzheimer’s and other neurodegenerative diseases led her to the Center for Innovation in Brain Science, where she is part of the AZ-TRADD program.
As a third-year MD/PhD student at the College of Medicine – Tucson, she is using skills gained through a U of A Health Sciences Data Science Fellowship to examine a gene that has been linked to Alzheimer’s: Apolipoprotein E, or APOE, and its allele APOE4. Though APOE e4 is a risk factor, some carriers may never develop the disease.
Tirambulo hopes to determine ways to predict who might develop the disease and how they might respond to treatment. This could lead to earlier diagnoses and better treatment options for those with Alzheimer’s.
“Coco is going into the data and asking precision medicine questions that could help people with an increased risk of Alzheimer’s: Can the data help lead us to an early intervention that could lower the risk factor for a person long before the disease develops?” Brinton said.
Tirambulo’s research seeks to identify at-risk patient profiles for potential drug development, ultimately hoping to determine if APOE e4 could be a novel therapeutic target.
“When I find commonalities in the data, I want to know what makes a person able to respond to a certain drug versus not respond. The goal is to find treatments that help improve everyone’s quality of life,” she said.
Tirambulo is on track to complete her MD/PhD in 2028. She envisions a future with treatments and even a cure for Alzheimer’s.
“Coco is one of the latest and greatest to come through our training program,” Brinton said. “Through her experiences growing up, she understands that when one person in the family has Alzheimer’s, the whole family has Alzheimer’s. That perspective inspires all of us.”
