COMBINING a blood biomarker with genetic information could improve predictions of cognitive impairment in adults at increased risk of Alzheimer’s disease, according to new research.
Plasma phosphorylated tau 217 (p-tau217) can become elevated before cognitive symptoms emerge. However, researchers found that considering apolipoprotein E (APOE) genotype alongside p-tau217 may provide additional information about both the risk and timing of cognitive impairment.
Researchers pooled participant-level data from seven multi-ethnic prospective cohorts in Canada, the Dominican Republic, and the USA. Participants were recruited through academic research centres and community settings between 1992–2025.
The baseline analysis included 8,582 adults with available p-tau217 measurements, cognitive assessments, APOE genotyping, and complete covariate data. Their mean age was 70 years and 65.9% were female. The cohort included 1,380 Black participants, 4,056 non-Hispanic White participants, and 3,146 participants of Hispanic or other ethnic origins.
A total of 4,569 participants had no cognitive impairment at baseline and were included in the longitudinal analysis. The primary outcome was cognitive impairment, defined as either mild cognitive impairment or dementia.
Higher p-tau217 concentrations were associated with prevalent cognitive impairment, with an odds ratio of 1.77. The association was stronger amongst carriers of the APOE-ε4 allele than non-carriers, with odds ratios of 2.25 and 1.52, respectively.
Baseline p-tau217 was also associated with future cognitive impairment. Each standard-deviation increase in the biomarker was linked to a 41% greater hazard of developing impairment.
When analysed according to APOE genotype, the association was again stronger amongst APOE-ε4 carriers. Each standard-deviation increase in p-tau217 was associated with a 76% greater hazard in carriers, compared with 26% in non-carriers.
Higher biomarker concentrations were also associated with a 24% shorter time to cognitive impairment amongst APOE-ε4 carriers and a 13% shorter time amongst non-carriers. Differences in impairment-free survival emerged approximately 3–4 years after biomarker assessment.
The findings suggest that two people with comparable p-tau217 concentrations may face different clinical trajectories depending on their APOE genotype. Combining the measures could therefore help identify at-risk individuals for closer monitoring or enrolment in prevention trials.
However, the results do not support routine testing of asymptomatic adults. The study measured p-tau217 at a single timepoint in most cohorts, and differences in assays and follow-up may have affected the findings. The outcome also included cognitive impairment from any cause rather than confirmed Alzheimer’s disease alone.
Further validation in broader international populations will be required before the combined approach can guide routine clinical decisions. Nevertheless, the researchers concluded that integrating blood biomarkers with genetic risk could support more personalised estimates of future cognitive decline.
Reference
Xu Y et al. Plasma phosphorylated tau 217 concentrations, APOE genotype, and timing of cognitive impairment in individuals across diverse racial and ethnic groups: a pooled analysis of prospective cohort studies. Lancet Neurol. 2026. DOI:10.1016/S1474-4422(26)00313-3.
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