Two-Step Blood Test Improved Alzheimer Disease Diagnosis and Predicted Cognitive Decline
KEY TAKEAWAYS
- Sequential plasma testing with %p-tau217 and eMTBR-tau243 improved identification of symptomatic Alzheimer disease.
- Positive eMTBR-tau243 results were associated with greater tau pathology and faster cognitive decline.
- The findings support a blood-based approach to improve Alzheimer disease diagnosis and patient stratification.
A sequential blood test strategy combining plasma %p-tau217 and eMTBR-tau243 improved diagnostic accuracy for symptomatic Alzheimer disease and identified individuals with greater tau pathology and faster cognitive decline. Among individuals with a positive %p-tau217 result, adding eMTBR-tau243 more accurately distinguished patients whose cognitive symptoms were attributable to Alzheimer disease pathology than %p-tau217 alone.
The BioFINDER-2 study (NCT03174938) enrolled 572 adults aged 40 years or older with subjective cognitive decline, mild cognitive impairment, or dementia from 2 Swedish memory clinics. Participants underwent plasma biomarker testing, amyloid and tau PET imaging or cerebrospinal fluid biomarker assessment, and longitudinal cognitive follow-up. Established Alzheimer disease required both a clinical Alzheimer disease phenotype and biomarker confirmation of amyloid and tau pathology. Findings were validated in an independent US cohort.
What the Study Found
- A total of 97% of participants with positive %p-tau217 had confirmed amyloid pathology, but only 57% met criteria for established Alzheimer disease.
- Among %p-tau217-positive participants, eMTBR-tau243 identified established Alzheimer disease with 81% accuracy, including an 84% positive predictive value and 77% negative predictive value.
- Positive eMTBR-tau243 status was associated with greater tau PET burden, faster tau accumulation, and greater cognitive decline.
- eMTBR-tau243 identified high tau burden with 87% accuracy and a 90% negative predictive value, outperforming %p-tau217.
The authors proposed using %p-tau217 to identify amyloid pathology followed by eMTBR-tau243 to determine whether Alzheimer disease pathology is likely contributing to cognitive symptoms. They noted that additional validation in more diverse populations and primary care settings is needed before widespread clinical implementation.
Source
Mattsson-Carlgren N, Palmqvist S, Horie K, et al. Integration of plasma eMTBR-tau243 and p-tau217 in the diagnosis and stratification of Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2026;25:357-367.