Research Suggests Key Protein Could Indicate Alzheimer’s Risk

A significant protein in the brain may help identify individuals at risk of developing Alzheimer’s disease later in life, according to a new study.

Researchers at Florida International University explored the protein TSPO, which acts as a biomarker for brain inflammation, to determine when and where its levels increase in the brain.

Using advanced imaging technology, they monitored TSPO in genetically modified mice that were predisposed to Alzheimer’s due to human gene mutations.

This mouse model is commonly used for studying the progression of the disease and testing potential therapies.

After assessing TSPO and Alzheimer’s levels in these mice, the scientists compared their findings with human brain samples donated by individuals from a large community in Colombia known for early-onset Alzheimer’s.

They found that TSPO levels were elevated in the subiculum, an essential part of the hippocampus, as early as six weeks old—roughly equivalent to ages 18 to 20 in humans.

Interestingly, microglia, which are the immune cells in the brain that gather around amyloid plaques, exhibited the highest TSPO levels. Amyloid plaques are notable markers of Alzheimer’s and are linked to cognitive decline and memory impairment.

In female mice, TSPO levels were particularly high, aligning with the statistic that about two-thirds of Alzheimer’s patients are women.

The brain tissue of Colombian patients, who bear a rare genetic mutation (PSEN1 E280A) often leading to early-onset Alzheimer’s, reflected similar patterns.

This suggests that high TSPO levels—observable through medical imaging—could signal a greater risk for developing Alzheimer’s.

Individuals with strong genetic predispositions showed elevated TSPO early on, hinting that brain inflammation might be a precursor to the disease.

The researchers aim to delve deeper into the role of TSPO, as they remain uncertain whether it contributes to brain damage or serves a protective function. They wonder if inhibiting or enhancing TSPO could slow the disease’s progression.

Lead investigator Dr. Tomás Guilarte noted, “This is the first study to seriously investigate how early this biomarker rises and where it begins to increase in the brain.”

He added that using this knowledge to push back Alzheimer’s development—even by a few years—could significantly enhance patients’ lives and decrease the condition’s prevalence.

Dr. Guilarte, a recognized authority on TSPO, has studied this protein for over thirty years, aiding in its identification as a viable imaging biomarker for diagnosing brain inflammation in various disorders.

Even at advanced Alzheimer’s stages, TSPO levels remained elevated in microglia near amyloid plaques.

The research team is currently using a specialized Alzheimer’s mouse model that lacks TSPO to further investigate these issues.

They also plan to include sporadic, late-onset Alzheimer’s cases, which account for over 90% of diagnoses.

Daniel Martínez Pérez, a Ph.D. candidate and primary author, expressed that, “The more we learn about these processes, the closer we get to customizing treatments that genuinely help—before it’s too late.”

He pointed out a considerable challenge in diagnosing Alzheimer’s: many view it purely as an age-related disease, which can delay diagnosis.

However, he emphasized that the disease begins long before symptoms appear, advocating for a broader range of biomarkers and therapeutic targets to enable personalized treatment options.

The Alzheimer’s Association estimates the number of Americans living with the disease will approach 13 million by 2050, with around seven million currently affected in the U.S. over the age of 65. Meanwhile, more than 100,000 fatalities annually are attributed to Alzheimer’s.

Early-onset Alzheimer’s affects a smaller population subset, with approximately five percent of early-onset cases diagnosed between 45 and 65 years of age—significantly earlier than the average diagnosis age of 80.

This form of Alzheimer’s is not merely a younger version of the disease; it often runs in families, sometimes passing down directly from parent to child, while other times it results from a combination of inherited genes that increase risk.

Typically, early-onset Alzheimer’s progresses more rapidly than later-onset cases. Despite accounting for the usual aging risks, those with early-onset diagnoses face a higher mortality rate due to various complications, including infections and seizures.

Complicating matters, the wide range of potential causes of death means accurately estimating the annual death toll linked to Alzheimer’s is challenging.

Nevertheless, around 120,000 individuals with Alzheimer’s—both typical and early-onset—reportedly died in 2022, based on the latest available data.