Portal U de A

By: Carlos Olimpo Restrepo S. Journalist from UdeA Communications Department  

TSPO could soon help predict Alzheimer's diagnosis decades before individuals begin to show symptoms, while also enhancing patients' quality of life by enabling more timely medical treatment. This biomarker is the latest discovery from a joint study by scientists from Florida International University and UdeA’s Antioquia Neurosciences Group. 

The Brain Bank of the Antioquia Neurosciences Group was key to the research. Photo: UdeA Communications Department / Alejandra Uribe F. 

Resources for detecting Alzheimer's disease before memory loss and other symptoms appear continue to advance. Recently, a group of researchers identified the TSPO biomarker, linked to brain inflammation, which increases significantly many years before the disease manifests. This conclusion was reached by experts from Florida International University (FIU) in collaboration with the Antioquia Neurosciences Group (GNA), affiliated with UdeA’s Faculty of Medicine. 

The discovery, published in the journal Acta Neuropathologica, opens the door to earlier diagnoses and the possibility of delaying Alzheimer's progression. "If we can use this information to delay the progression of the disease by even five years, we could significantly improve patients' quality of life and reduce prevalence," explained Tomás R. Guilarte, principal investigator and dean of the FIU College of Public Health. 

"This discovery is of enormous importance. This technique for early detection of proteins like TSPO will allow us, in the future, to intervene much sooner in the treatment of the disease and provide much more appropriate patient management," said Carlos Andrés Villegas Lanau, coordinator of the GNA Neurobank. 

For the study, two key sources were analyzed: genetically modified mice—technically called murine models—that develop Alzheimer's disease; and brain tissue donated by families from Antioquia carrying the so-called "Paisa mutation," considered the largest group in the world with a predisposition to this early-onset disease. This variant, identified by the late neurologist Francisco Lopera Restrepo, causes symptoms starting around age 40 and usually leads to death by age 60. 

"In our community, thanks to studies conducted by GNA, we have identified numerous family groups with mutations that lead to the development of the disease. Therefore, in these individuals, the risk of developing it can be identified from a very early age," highlighted researcher Villegas Lanau, who added that markers such as TSPO can help assess the progression of Alzheimer's. 

The research results showed that TSPO increases at very early stages, as early as 18 or 20 years of age in humans. The increase was primarily observed in microglia, cells that perform defensive functions in the brain and are often clustered around plaques associated with Alzheimer's disease. Furthermore, female mice had higher levels, which is consistent with a previously established reality: two out of three Alzheimer's patients are women. 

The discovery does not yet resolve whether TSPO plays a harmful or protective role in the brain, but it does raise valuable questions: Could blocking or enhancing it change the course of the disease? To find answers, researchers are now working with a special mouse model that lacks this biomarker and are expanding the study to the most common cases of Alzheimer's disease, late-onset Alzheimer's, which account for more than 90% of diagnoses. 

Differences with current methods 

This discovery also paves the way for future early diagnosis methods or techniques, which are vital for enabling more timely interventions for patients. Currently, for example, early detection of Alzheimer's disease relies on memory tests or imaging to detect proteins called beta-amyloid or TAU, which are involved in the development of the condition. 

In contrast, TSPO is directly associated with the brain's immune response and microglia activity. "This is leading us directly to an immune response because it has an important relationship with microglia. This is what differentiates it from other early disease detection methods," Villegas Lanau indicated. 

This doctor, an expert in neurodegenerative diseases, indicated that clinical tests are complemented with positron emission tomography (PET) for a more accurate diagnosis. This high-precision technique allows doctors to confirm the presence and severity of the disease. "We must keep in mind that, currently, several of the treatment perspectives are specifically directed at an immune response that can reduce these protein deposits that have been associated with causing the disease," emphasized Carlos Andrés Villegas Lanau. 

"The more we understand these processes, the closer we'll be to designing treatments that can actually help before it's too late," said Daniel Martínez Pérez, first author of the study and a PhD candidate in Guilarte's lab at FIU.