A new study led by Tomás R. Guilarte, dean of the Robert Stempel College of Public Health & Social Work at Florida International University (FIU), has identified a potential early biomarker for Alzheimer’s disease. The research focuses on TSPO, a protein that may be detectable in the brain before the onset of memory loss or cognitive decline.
“Neuroinflammation is a very early event in Alzheimer’s that influences its onset,” said Guilarte. “If we can use TSPO to detect it early, right at the beginning stages of the disease, it could mean slowing progression or delaying symptoms by five or six years. That’s five or six years where someone has a better quality of life.”
TSPO, which stands for translocator protein 18 kDa, is typically present at low levels in the brain. According to Guilarte, when neuroinflammation occurs, TSPO levels increase and continue to rise as inflammation spreads. This activity can be visualized on PET scans.
Guilarte’s previous work demonstrated elevated TSPO levels in active and recently retired NFL players between ages 23 and 39. He was among the first scientists to validate TSPO as a marker for neuroinflammation during his time at Johns Hopkins University in the 1990s. Today, researchers worldwide use TSPO to monitor inflammation related to various neurological and psychiatric diseases.
In this latest study published in Acta Neuropathologica, FIU researchers used advanced imaging technology to determine where and when TSPO appears in the brain. They found that increased TSPO coincided with early amyloid plaque formation in the subiculum region of the hippocampus—a key area for learning and memory.
The team also examined which glial cells were producing TSPO signals. They discovered that microglia located near amyloid plaques had higher concentrations of TSPO than other cells such as astrocytes.
“We didn’t see any TSPO increase in the other glial cells, like the astrocytes, which reveals the microglia are driving the majority of the inflammatory response,” said Guilarte. “What we believe is happening is something goes wrong with the microglia. They stop doing their job in removing the plaques and just keep sending out TSPO signals. This constant signal of neuroinflammation is like adding wood to a fire.”
Human brain tissue from patients with Alzheimer’s disease showed similar patterns. The samples were donated by individuals from Medellín and nearby areas in Colombia who have inherited an early-onset form of Alzheimer’s known as the Paisa mutation.
Daniel Martinez-Perez, first author of the study and doctoral candidate at FIU, credited collaboration with Colombian partners: “This work and our future projects would not be possible without our collaborators in Colombia, the patients and their families that make an essential contribution to study Alzheimer’s,” he said. “Dr. Lopera was really interested in finding ways to prevent this disease, among them the role of neuroinflammation and other mechanisms of Alzheimer’s, so we are so proud to carry on the legacy of his life’s work with this study.”
Although this research focused on genetic forms of early-onset Alzheimer’s disease, Guilarte believes neuroinflammation plays a significant role across all types—including late-onset cases.
Martinez-Perez has begun analyzing human brain samples from late-onset cases as part of ongoing studies at Universidad de Antioquia’s neuroscience group.
“One of the biggest problems with Alzheimer’s is people see it as a disease of aging and that impacts when people get diagnosed,” Martinez-Perez said. “But the reality is that the disease starts decades before diagnosis and the more biomarkers and therapeutic targets our global community of scientists are finding, the closer we all get to physicians having a whole panel of diagnostics to be able to deliver more personalized, tailored treatments. My hope is we can be part of helping people before they are too sick.”
