• Two-step blood testing improves clinical attribution: p-tau217 identifies Aβ pathology, while eMTBR-tau243 helps determine whether Alzheimer’s pathology is actually driving symptoms, reducing misclassification of asymptomatic cases.
• p-tau217 alone risks overdiagnosis: among p-tau217-positive patients, only 57% had established Alzheimer’s disease, underscoring limited specificity for symptomatic disease.
• eMTBR-tau243 improves diagnostic performance: in p-tau217-positive individuals, it achieved ~81% accuracy and ~84% positive predictive value for identifying established Alzheimer’s disease.
• Biomarker profiles reflect disease progression: eMTBR-tau243 positivity is associated with higher tau burden, faster tau accumulation, and worse longitudinal cognitive decline.
• Clinical utility extends to treatment decisions: the combined workflow may reduce reliance on PET/CSF testing, enable cost-effective triage, and help identify patients with high tau burden who may respond differently to anti-amyloid therapies.

Source: Nature Medicine