TSPO, a key biomarker of brain inflammation, could help detect Alzheimer's disease years before memory loss and other symptoms set in - potentially leading to advances in how the disease is diagnosed and treated, according to a study published in Acta Neuropathologica.
"This is the first study to really examine how early this biomarker increases and where it begins rising in the brain," said Tomás R. Guilarte, lead researcher and dean of FIU's Robert Stempel College of Public Health & Social Work. "If we can use this information to help delay Alzheimer's progression by even five years, it can drastically improve patients' lives and reduce disease prevalence."
Guilarte, an internationally established expert on TSPO (or translocator protein 18 kDa) has studied the protein for more than three decades. His work helped establish it as a reliable imaging biomarker used in diagnosing neuroinflammation in various neurodegenerative, neurological and psychiatric disorders.
For this study, Guilarte and his team used advanced imaging software to track TSPO levels in genetically engineered mouse models of familial Alzheimer's and confirmed their findings using human brain tissue donated by members of the world's largest group of individuals with early-onset familial Alzheimer's, located in Antioquia, Colombia.
These families carry the "paisa" mutation, identified by the late Dr. Francisco Lopera, one of the authors of the study, who remained dedicated to finding ways to prevent Alzheimer's disease. For carriers of this mutation, symptoms typically begin in their 30s to 40s; they die in their 50s.
In the mouse model, researchers detected elevated TSPO levels in the subiculum - a critical part of the hippocampus - as early as six weeks of age, roughly equivalent to age 18-20 in humans. Microglia, the brain's main immune cells, specifically those clustered around amyloid plaques, had the highest levels of TSPO. Notably, female mice had higher TSPO levels, mirroring real-world statistics: two-thirds of Alzheimer's patients are women.
The brain tissue samples from the Colombian patients with the paisa mutation showed the same pattern. Even in late-stage Alzheimer's, TSPO remained high in microglia near plaques. These results raise new questions about TSPO's function - whether it contributes to damage or protects the brain - and whether blocking or enhancing it could halt disease progression.
The team is now working with a specially developed Alzheimer's mouse model lacking TSPO to explore these questions further. They're also expanding the study to include sporadic, late-onset Alzheimer's cases, the form that accounts for over 90% of all diagnoses.
"The more we understand these processes," said Daniel Martínez Pérez, first author and Ph.D. candidate in Guilarte's lab, "the closer we get to tailoring treatments that can truly help - before it's too late."
TSPO, a key biomarker of brain inflammation, could help detect Alzheimer's disease years before memory loss and other symptoms set in - potentially leading to advances in how the disease is diagnosed and treated, according to a study published in Acta Neuropathologica.
"This is the first study to really examine how early this biomarker increases and where it begins rising in the brain," said Tomás R. Guilarte, lead researcher and dean of FIU's Robert Stempel College of Public Health & Social Work. "If we can use this information to help delay Alzheimer's progression by even five years, it can drastically improve patients' lives and reduce disease prevalence."
Guilarte, an internationally established expert on TSPO (or translocator protein 18 kDa) has studied the protein for more than three decades. His work helped establish it as a reliable imaging biomarker used in diagnosing neuroinflammation in various neurodegenerative, neurological and psychiatric disorders.
For this study, Guilarte and his team used advanced imaging software to track TSPO levels in genetically engineered mouse models of familial Alzheimer's and confirmed their findings using human brain tissue donated by members of the world's largest group of individuals with early-onset familial Alzheimer's, located in Antioquia, Colombia.
These families carry the "paisa" mutation, identified by the late Dr. Francisco Lopera, one of the authors of the study, who remained dedicated to finding ways to prevent Alzheimer's disease. For carriers of this mutation, symptoms typically begin in their 30s to 40s; they die in their 50s.
In the mouse model, researchers detected elevated TSPO levels in the subiculum - a critical part of the hippocampus - as early as six weeks of age, roughly equivalent to age 18-20 in humans. Microglia, the brain's main immune cells, specifically those clustered around amyloid plaques, had the highest levels of TSPO. Notably, female mice had higher TSPO levels, mirroring real-world statistics: two-thirds of Alzheimer's patients are women.
The brain tissue samples from the Colombian patients with the paisa mutation showed the same pattern. Even in late-stage Alzheimer's, TSPO remained high in microglia near plaques. These results raise new questions about TSPO's function - whether it contributes to damage or protects the brain - and whether blocking or enhancing it could halt disease progression.
The team is now working with a specially developed Alzheimer's mouse model lacking TSPO to explore these questions further. They're also expanding the study to include sporadic, late-onset Alzheimer's cases, the form that accounts for over 90% of all diagnoses.
"The more we understand these processes," said Daniel Martínez Pérez, first author and Ph.D. candidate in Guilarte's lab, "the closer we get to tailoring treatments that can truly help - before it's too late."
Read more https://www.sciencedaily.com/releases/2025/09/250922074952.htm