Alzheimer's Blood Marker Tracks Brain Amyloid Similarly Across Groups, but Baseline Levels Differ, Study Finds

A JAMA Neurology analysis of more than 15,000 screening participants finds the %p-tau217 blood test relates to brain amyloid in largely the same way across racial and ethnic groups, even though the raw biomarker levels themselves run lower in Asian, Black and Hispanic participants.

A cross-sectional analysis of 15,612 cognitively unimpaired adults screened for an Alzheimer's prevention trial found that higher blood levels of plasma phosphorylated tau 217 percentage, or percent p-tau217, tracked with higher brain amyloid on PET scans in broadly similar fashion across Asian, Black and White participants, and across Hispanic and non-Hispanic participants. The study, published online October 12 in JAMA Neurology by researchers at the Keck School of Medicine of the University of Southern California, also found that the raw percent p-tau217 levels themselves ran lower in Asian, Black and Hispanic participants than in White and non-Hispanic participants, a separate finding from the strength of the amyloid relationship itself.

The data come from screening for the AHEAD 3-45 trial, which is testing whether the anti-amyloid drug lecanemab can delay cognitive decline in people who have no Alzheimer's symptoms but carry brain amyloid. Researchers analyzed screening results collected from July 2020 to October 2024 at 106 sites across Asia, Australia, Europe and North America, in adults ages 55 to 80, before medical or cognitive exclusions were applied. The cohort's mean age was 68.4, almost 64 percent were female, and about 37 percent carried at least one copy of the APOE e4 gene variant, the best-known genetic risk factor for Alzheimer's disease. This builds on an earlier line of pTau217 reporting, including findings that the same blood marker can also rise in two unrelated amyloid diseases, by turning to the specific question of whether the test performs equally well as a trial-screening tool across different populations.

Carrying the APOE e4 variant was associated with higher percent p-tau217 levels in every racial and ethnic group studied, but the size of that association differed significantly by race and by ethnicity, according to the paper. The relationship between percent p-tau217 and amyloid PET scans, and between the marker and a cognitive composite score, showed no significant differences when compared pairwise across the three racial groups, but did differ by Hispanic versus non-Hispanic ethnicity. The study's corresponding author, Doris P. Molina-Henry of the Alzheimer's Therapeutic Research Institute at USC, said in a university statement that "the relationship between the biomarker and brain amyloid was generally consistent across racial groups," even as absolute levels varied.

The researchers said the lower baseline biomarker levels in historically underrepresented groups raise open questions about what drives those differences and whether they bear on dementia risk, questions this screening analysis was not designed to answer.