By the time Alzheimer’s disease is diagnosed in most patients, a cascade of changes has already taken place in the brain. Understanding what these changes are could pave the way for better detection and treatment for a progressive disease that can be managed and slowed, but not cured.
Local scientists with Texas Biomedical Research Institute and UT Health San Antonio hope to pull back the curtain on what drives both Alzheimer’s disease and the typical neurodegeneration that comes with old age.
With the help of $200,000 in grant funding from the San Antonio Medical Foundation, the researchers will study the brains of aging baboons at Texas Biomed’s Southwest National Primate Research Center.
“This is a hugely important question about brain aging specifically and aging more generally,” said Adam Salmon, associate director of the Sam and Ann Barshop Institute for Longevity and Aging Studies at the UT San Antonio Health Science Center. “With this team, this project has been a great opportunity to think about how the models we use can help benefit actual clinical translation.”
Alzheimer’s is a neurodegenerative disease that slowly erodes memory and thinking. Around 7.4 million Americans 65 years and older live with it, and South Texas is home to some of the highest Alzheimer’s rates in the country.
Scientists know a lot about what raises a person’s risk of developing Alzheimer’s disease, from genetics to high blood pressure and head trauma. But researchers can’t fully explain what’s happening inside the brain and driving the disease.
Two proteins known as beta-amyloid and tau are the leading suspects.
Beta-amyloid plaques build up inside diseased brains, often many years before symptoms begin. Tau proteins, on the other hand, change shape inside nerve cells and become tangled. Both are considered hallmark signs of Alzheimer’s disease, but as the local researchers explained, the picture is incomplete.
“It’s unclear to what degree the amyloids are causative or an end product,” said Eric Vallender, associate director for research at Texas Biomed’s primate center. “There’s a lot of other stuff happening in the brain other than the amyloid plaques and tau aggregates. We want to understand what else is happening.”
To do that, researchers will take small samples of brain tissue from aging baboons — primates whose brains are quite similar to the human brain — and use a new method of mapping proteins in tissue known as spatial proteomics to understand what’s happening at the molecular level.
The brain biopsies will be accompanied by cognitive testing and blood biomarkers to get an idea of how these metrics, which are used to diagnose the disease in humans, compare to what’s actually happening inside the brains of the baboons.
Vallender is interested in better understanding the role of the blood-brain barrier, a selective cell lining that controls what passes from the bloodstream to the brain, in normal brain aging as well as diseases like Alzheimer’s. This cell lining can break down as we age, potentially contributing to inflammation and cell death.
Kimberley Phillips, a psychology professor at Trinity University and brain aging researcher who also works at Texas Biomed, hopes to shed light on the role the brain’s support cells, — glial cells — play in neurodegeneration.
“The ultimate goal is earlier detection,” she said, “allowing then for earlier interventions that might either alter the course or at least delay the course of progression.”
Currently, testing for Alzheimer’s disease is typically reserved for patients already exhibiting symptoms, even though the disease process starts long before then. Finding new ways to detect the disease on the molecular level in its preclinical phase is a big priority for researchers, as it could also lead to targeted treatments.
Two treatments for Alzheimer’s were approved by the U.S. Food and Drug Administration in 2023 and 2024: Leqembi and Kisunla. Both drugs slow progression of Alzheimer’s in its earlier stages by targeting beta-amyloid plaque in the brain, but they cannot reverse the course of the disease.
Salmon, who studies the biology of aging, wants to understand how cell mitochondria — responsible for maintaining energy in the cell — are involved in the aging and neurodegenerative process.
“If you could preserve those cells and preserve their function, you’re going to preserve cognitive function,” Salmon said.
The researchers will use the initial grant funding to run a pilot study over the next year and then look to receive additional funding for more research.
“Whether it’s based on mitochondrial function or based on something of the proteomics we’re looking at,” Salmon added, “that would be huge for the field because now you could intervene before those symptoms actually happen.”
