Blood-Based p-tau217/Amyloid β 1-42 Test May Improve Diagnostic Confidence in Alzheimer Disease

A plasma biomarker ratio combining phosphorylated tau 217 (p-tau217) and amyloid-beta 1-42 (Aβ 1-42) demonstrated improved accuracy and reduced diagnostic uncertainty for detecting amyloid pathology, according to a study published in Brain. In a press release from Fujirebio Diagnostics (Malvern, PA), the company stated that the published findings support the clinical utility of the Lumipulse G p-tau217/Aβ 1-42 (Fujirebio Diagnostics, Malvern, PA) plasma ratio as a blood-based biomarker for the diagnosis of Alzheimer disease (AD), offering enhanced performance compared with p-tau217 alone and reducing the proportion of indeterminate test results in symptomatic patients.

The study, supported by Fujirebio Diagnostics, evaluated plasma biomarkers against established reference standards for amyloid pathology. Diagnostic thresholds were derived using both cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) imaging. The study investigators applied a clearly defined, 2-cutoff framework, with separate thresholds established to identify individuals likely to have amyloid pathology and those unlikely to have amyloid pathology. Results falling between these cutoffs were classified as indeterminate. This approach was intended to reflect real-world clinical decision-making in secondary care settings, balancing sensitivity and specificity while minimizing inconclusive results.

Key findings from the study include the following:

• The plasma p-tau217/Aβ 1-42 ratio demonstrated superior diagnostic performance for detecting amyloid pathology compared with plasma p-tau217 alone, with an area under the receiver operating characteristic curve (AUC) of 0.932 (95% CI, 0.896 to 0.967) vs 0.918 (95% CI, 0.880 to 0.956) for p-tau217 alone (P<.001).
• The p-tau217/Aβ 1-42 ratio achieved 84% sensitivity and 95% specificity compared with 81% sensitivity and 93% specificity for plasma p-tau217 alone.
• Using a 2-threshold (3-category) approach based on predefined positive and negative likelihood ratio targets (PLR/NLR 14/20), the p-tau217/Aβ 1-42 ratio achieved a positive predictive value (PPV) of 94.4% and a negative predictive value (NPV) of 94.3% in the parametric model.
• The 2-threshold strategy substantially reduced indeterminate results with the p-tau217/Aβ 1-42 ratio compared with p-tau217 alone (26.5% vs 38.6% in the parametric analysis and 20.2% vs 35.1% in the nonparametric analysis).
• Biomarker performance for the pTau217/Aβ1-42 ratio was consistent across age, sex, and APOE ε4 carrier status, with no significant interaction between APOE ε4 status and amyloid positivity (interaction P=.28).
• Biomarker performance for the p-tau217/Aβ 1-42 ratio was consistent across age, sex, and apolipoprotein (APOE) ε4 carrier status, with no significant interaction between APOE ε4 status and amyloid positivity (interaction P=.28).
• Cutpoints derived using both CSF biomarkers and amyloid PET showed alignment across reference standards.

Source: Benina N, Buitrago L, De Simone FI, et al. Plasma pTau 217:β-amyloid 1-42 ratio for enhanced accuracy and reduced uncertainty in detecting amyloid pathology. Brain. Published January 21, 2026. Accessed January 23, 2026. https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awag001/8435032?login=false

Fujirebio Diagnostics. Fujirebio announced the publication of a landmark study in Brain (Oxford Academic): “plasma pTau 217/Aβ 1-42 ratio for enhanced accuracy and reduced uncertainty in detecting amyloid pathology.” Fujirebio. Published January 21, 2026. Accessed January 23, 2026. https://www.fujirebio.com/en-us/news-events/fujirebio-announced-the-publication-of-a-landmark-study-in-brain-oxford-academic-plasma