A study of more than 15,000 adults found that the blood biomarker remained consistently associated with brain amyloid despite differences in baseline levels across racial and ethnic groups.
A global study evaluating 15,612 cognitively unimpaired adults has demonstrated that blood-based testing for the plasma phosphorylated tau 217 percentage (%p-tau217) reliably identifies elevated brain amyloid across diverse racial and ethnic groups, providing crucial validation for clinical laboratories and trial investigators utilizing blood biomarkers as initial screening tools.
The findings, led by researchers at the Keck School of Medicine of USC and published in JAMA Neurology, found that while baseline biomarker levels varied by demographic group, higher %p-tau217 values consistently correlated with elevated brain amyloid across racial cohorts.
“We found that %p-tau217 levels were lower in populations that have historically been underrepresented in clinical trials. Importantly, however, the relationship between the biomarker and brain amyloid was generally consistent across racial groups,” says Doris P Molina-Henry, PhD, study corresponding author and associate professor of research neurology with the Epstein Family Alzheimer’s Therapeutic Research Institute at the Keck School of Medicine of USC, in a release. “This supports the use of blood-based biomarkers as an initial screening tool for elevated amyloid in a preclinical Alzheimer’s disease trial.”
Biomarker Performance in Trial Screening
The investigation analyzed screening data from the AHEAD 3-45 clinical trials, which evaluate whether the monoclonal antibody lecanemab can delay cognitive decline in asymptomatic individuals with brain amyloid. Screening was conducted across 106 research sites in Asia, Australia, Europe, and North America in adults aged 55 to 80.
In the screening protocol, participants first underwent blood testing for the plasma phosphorylated tau 217 percentage (%p-tau217), the proportion of circulating tau carrying the Alzheimer’s-related phosphorylation at position 217. Individuals meeting prespecified biomarker criteria then proceeded to confirmatory positron emission tomography (PET) imaging to verify brain amyloid deposition.
The analysis revealed notable baseline differences: %p-tau217 concentrations were generally lower among Asian and Black participants compared with White participants, as well as lower among Hispanic participants compared with non-Hispanic participants. Despite these baseline disparities, higher %p-tau217 measurements maintained a direct, consistent association with elevated amyloid pathology on PET scans across all racial groups.
Correlation with Genetic Risk and Broader Dementia Factors
The researchers also evaluated how biomarker levels interacted with known genetic determinants. Carriers of the APOE ε4 allele, a major genetic risk factor for Alzheimer’s disease, exhibited higher levels of %p-tau217 than non-carriers, a relationship that persisted across racial and ethnic groups.
“These findings reinforce the relationship between APOE ε4 and Alzheimer’s-related blood biomarkers, while showing that the strength of this relationship can vary across populations,” says Molina-Henry in a release.
The observed baseline variations highlight critical diagnostic considerations for laboratorians and clinicians interpreting blood-based biomarker assays. While Black and Hispanic participants demonstrated lower circulating %p-tau217 levels, epidemiological evidence indicates these populations have historically faced a higher overall incidence of dementia.
“These findings remind us that dementia risk is complex and may involve multiple contributing factors beyond Alzheimer’s-related changes measured by this blood test or a PET scan,” says Molina-Henry in a release. “Other processes in the brain may also play a role—and that warrants further study.”
To assess biomarker trajectories over time, researchers are continuing longitudinal assessments through the Alzheimer’s Plasma Extension Study (APEX), which monitors individuals screened during AHEAD 3-45 who did not meet trial amyloid cutoffs using serial plasma assays, PET imaging, and cognitive evaluations.
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