Automated p-tau217 test identifies amyloid pathology in Taiwanese memory clinic

A fully automated plasma assay for phosphorylated tau 217, or p-tau217, showed high diagnostic accuracy for identifying brain amyloid beta pathology in a Taiwanese memory-clinic cohort, according to a single-center cross-sectional study that evaluated 139 adults. The Roche Elecsys p-tau217 assay achieved an area under the receiver operating characteristic curve of 0.973 in the primary threshold-analysis cohort of 135 participants. A two-threshold strategy assigned 88.1% of participants to definitive negative or positive zones, with an overall agreement of 95.0% among people in those zones. The researchers said the candidate thresholds require independent external validation before they can be adopted for routine clinical use.

Participants were recruited from the memory clinics of Taipei Veterans General Hospital and received physical examinations, clinical interviews, neuropsychological testing and brain magnetic resonance imaging. Brain amyloid status was established using amyloid positron emission tomography in 136 participants and cerebrospinal fluid biomarkers in three; no participant underwent both reference-standard methods. Amyloid PET used 18F-florbetaben, with positivity defined as a Centiloid value of at least 20. The cerebrospinal fluid reference standard used the manufacturer-recommended p-tau181/Aβ42 ratio cutoff of greater than 0.023. The primary threshold analysis excluded four extreme statistical values and included 76 amyloid-negative and 59 amyloid-positive participants. Ages ranged from 50 to 85 years, and 70 of the 139 participants were female.

The investigators derived two possible decision rules from the primary cohort. Concentrations below 0.225 picograms per milliliter, or pg/mL, were designated the Negative Zone, while concentrations above 0.336 pg/mL were designated the Positive Zone. Values between the two thresholds formed an Intermediate Zone, where the result was treated as uncertain and potentially requiring confirmatory evaluation. The lower cutoff was intended to prioritize sensitivity for ruling out amyloid pathology, and the upper cutoff was intended to prioritize specificity for ruling it in. Of the 135 participants, 65 were classified as negative, 54 as positive and 16, or 11.9%, as intermediate. Within the two definitive zones, 95.0% of classifications agreed with the reference standard, with a 95% confidence interval of 89.3% to 98.1%.

For comparison, the researchers also evaluated a single threshold of 0.251 pg/mL, selected from the observed receiver operating characteristic curve to maximize the Youden index, defined as sensitivity plus specificity minus one. At that cutoff, positive percent agreement for amyloid positivity was 93.2%, with a 95% confidence interval of 83.5% to 98.1%, and negative percent agreement was 89.5%, with a 95% confidence interval of 80.3% to 95.3%. Overall agreement was 91.1%, with a 95% confidence interval of 85.0% to 95.3%. The analysis also included 1,000 bootstrap resamples, which yielded a median area under the curve of 0.975 and a 95% percentile interval of 0.947 to 0.992. The resampling indicated stable discrimination, but the threshold estimates varied, so the precise numerical cutoffs should be regarded as cohort-derived estimates rather than established clinical standards.

Sensitivity analyses produced broadly similar results when the four excluded measurements were restored. In the full group of 139 participants, the area under the curve was 0.954, with a 95% confidence interval of 0.920 to 0.989. The single threshold remained 0.251 pg/mL, while the upper dual cutoff changed to 0.400 pg/mL. Under this analysis, 86.3% of participants received definitive classifications, 13.7% remained in the Intermediate Zone and agreement within the definitive zones was 94.2%. Restricting the analysis to the 136 participants assessed by amyloid PET produced an area under the curve of 0.955, with a 95% confidence interval of 0.921 to 0.990, definitive classifications for 86.8% and agreement of 94.1% within those zones. In an analysis of 79 participants who were cognitively unimpaired or had mild cognitive impairment, the area under the curve was 0.937, although a small number of amyloid-positive cases limited the precision of the estimate.

Head-to-head comparisons were possible in 81 participants with complete measurements for every biomarker. In that subgroup, the automated Roche p-tau217 assay produced an area under the curve of 0.970, with a 95% confidence interval of 0.939 to 1.000, while the research-grade Simoa p-tau217 assay produced 0.957, with a 95% confidence interval of 0.915 to 0.998. The difference was not statistically significant, with a p value of 0.097. Both p-tau217 assays had higher areas under the curve than Roche p-tau181 and neurofilament light chain, or NfL. Roche p-tau181 achieved 0.880, with a 95% confidence interval of 0.800 to 0.961, while NfL achieved 0.615, with a 95% confidence interval of 0.494 to 0.737. The comparison was limited to complete cases, and that subgroup had fewer amyloid-positive participants, fewer APOE ε4 carriers and fewer participants with dementia than the rest of the cohort.

The concentration of Roche p-tau217 was also strongly associated with amyloid status. Each one-standard-deviation increase in log-transformed p-tau217 was associated with amyloid positivity in the unadjusted model, with an odds ratio of 26.71 and a 95% confidence interval of 9.67 to 73.75. The association remained after adjustment for age, sex, body mass index, estimated glomerular filtration rate, or eGFR, and APOE ε4 carrier status, with an adjusted odds ratio of 30.34 and a 95% confidence interval of 7.85 to 117.23. There was no statistically significant interaction between p-tau217 and clinical diagnosis. Lower eGFR was independently associated with higher p-tau217 concentrations in multivariable linear regression, but adding eGFR to the diagnostic model did not significantly improve discrimination of amyloid positivity: the area under the curve changed from 0.973 to 0.980, with a p value of 0.204.

Several features of the study limit how far its results can be generalized. It was a single-center, cross-sectional study with a modest sample, and the proposed thresholds were both derived and evaluated in the same population, which may make their apparent performance more favorable than performance in an independent cohort. Clinical diagnoses were also unevenly distributed. The amyloid-negative group included 47 cognitively unimpaired participants, 17 with mild cognitive impairment and 12 with dementia, whereas the amyloid-positive group included five cognitively unimpaired participants, 10 with mild cognitive impairment and 44 with dementia. Most participants had preserved or mildly impaired kidney function, and none had severe chronic kidney disease, limiting conclusions about interpretation in advanced renal impairment. The study also did not evaluate sample stability, interlaboratory reproducibility, population screening or whether amyloid PET and cerebrospinal fluid confirmation could safely be omitted.

Taken together, the findings show that the automated assay separated amyloid-positive and amyloid-negative participants with high accuracy in this memory-clinic population, while the dual-threshold scheme left a minority of results in an intermediate category. The study did not measure whether using that scheme would reduce confirmatory testing, diagnostic delays, costs or clinically consequential misclassification, and it did not establish that the Roche and Simoa platforms are interchangeable. Prospective multicenter studies would need to validate the candidate cutoffs in larger, more diverse and earlier-stage populations, assess real-world testing pathways, and determine how renal impairment and other systemic factors should affect interpretation. Until those data are available, the reported thresholds are best viewed as a promising basis for further validation rather than ready-made rules for routine diagnosis.

Subject of Research: Clinical performance of an automated plasma p-tau217 assay for detecting brain amyloid pathology in a Taiwanese memory-clinic cohort

Article Title: Clinical performance and decision thresholds of an automated plasma p-tau217 assay for amyloid pathology in a Taiwanese memory clinic

Article References: Lin, Y.-S., Tsai, M.-J., Lai, C.-L., Ho, H.-L., & Fuh, J.-L. (2026). Clinical performance and decision thresholds of an automated plasma p-tau217 assay for amyloid pathology in a Taiwanese memory clinic. Journal of Neurology, 273(11), Article 674. https://doi.org/10.1007/s00415-026-14193-2

Image Credits: AI Generated

DOI: 10.1007/s00415-026-14193-2

Keywords: Alzheimer's disease, amyloid pathology, p-tau217, blood biomarkers, plasma assay, amyloid PET, memory clinic, diagnostic accuracy, decision thresholds, Taiwan, Clinical, performance