Early brain inflammation biomarker TSPO shows up years before Alzheimer's symptoms, study finds

A biomarker in the brain that flags inflammation could reveal who is likely to develop Alzheimer's years before symptoms appear, a new study suggests. Researchers from Florida International University examined TSPO, a protein that marks brain inflammation, in mice genetically engineered to carry human mutations known to increase Alzheimer's risk, and then compared the findings with human brain tissue donated by members of Colombia’s Paisa family, which carries a rare early-onset form of the disease.

In the mouse model, elevated TSPO appeared in the subiculum, a key region of the hippocampus, as early as six weeks of age—roughly equivalent to ages 18 to 20 in humans. Microglia, the brain’s immune cells that cluster around amyloid plaques, showed the highest TSPO levels. Notably, female mice exhibited higher TSPO levels, echoing real-world statistics that two-thirds of Alzheimer's patients are women. The brain tissue from Paisa mutation carriers with PSEN1 E280A showed the same pattern, suggesting the imaging biomarker could indicate higher risk in humans with a strong genetic predisposition.

Lead researcher Dr. Tomás Guilarte said this is the first study to really examine how early this biomarker increases and where it begins rising in the brain. “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,” he said. Guilarte is an internationally recognized expert on TSPO, a protein he has studied for more than three decades, helping establish its role as a reliable imaging biomarker for brain inflammation across neurodegenerative and psychiatric disorders. Even in late-stage Alzheimer’s, the researchers found TSPO remained high in microglia near amyloid plaques. The team is now working with a specially developed Alzheimer's mouse model lacking TSPO to explore these questions further and plans to expand the study to include sporadic, late-onset Alzheimer’s cases that account for more than 90 percent of diagnoses.

Daniel Martínez Pérez, the study’s first author and a Ph.D. candidate in Guilarte’s lab, said understanding these processes brings researchers closer to tailoring treatments before patients are too sick. “The more we understand these processes, the closer we get to physicians having a whole panel of diagnostics to deliver more personalized, tailored treatments,” he said. “One of the biggest problems with Alzheimer’s is people see it as a disease of aging, which affects when people get diagnosed. But the disease starts decades before diagnosis.”

Alzheimer’s is one of the most common forms of dementia and primarily affects adults over 65. About seven million Americans 65 and older live with the condition, and over 100,000 die from it annually. The Alzheimer’s Association projects that by 2050, nearly 13 million Americans will be living with the disease. Early-onset Alzheimer’s affects a smaller subset of the population, typically diagnosed between ages 45 and 65 and often running in families. It tends to progress more rapidly than late-onset disease, and deaths in this group occur at higher-than-average rates even after accounting for age. While precise death tolls are difficult to pin down due to the disease’s varied causes, the 2022 death total for Alzheimer’s, including both typical and early-onset cases, was around 120,000 in the United States.