# Plasma Phosphorylated Tau 217 Cutoffs for Amyloid Pathology and Kidney Function, Body Mass Index, and Anemia

## TL;DR

The study compares different cutoff strategies for plasma p-tau217 to detect amyloid-β positivity, finding that subgroup-specific cutoffs improve accuracy and cost efficiency in certain conditions like chronic kidney disease and anemia.

## Contribution

The study introduces subgroup-specific cutoffs for plasma p-tau217 testing, showing improved diagnostic accuracy and cost efficiency in specific biological subgroups.

## Key findings

- Subgroup-specific optimal cutoffs improved accuracy over standard single cutoffs in chronic kidney disease and anemia.
- Double cutoffs showed higher accuracy in obesity but introduced intermediate results.
- Optimal cutoffs provided better cost efficiency in chronic kidney disease compared to double cutoffs.

## Abstract

This cohort study compares the performance of 3 plasma p-tau217 classification strategies for detecting amyloid-β positivity to consider which offers better optimize diagnostic accuracy and cost efficiency.

For plasma phosphorylated tau 217–based amyloid-β detection, does the strategy of using biological subgroup–specific optimal single cutoffs or a double cutoff better optimize diagnostic accuracy and cost efficiency?

This cohort study found that subgroup-specific optimal cutoffs improved accuracy over the standard single cutoff, especially in chronic kidney disease (CKD) and anemia. Compared with a double cutoff, the optimal cutoff had similar or better accuracy in CKD with lower cost, whereas a double cutoff was slightly better in underweight and anemia but created intermediates; in obesity, a double cutoff remained superior.

Biologically optimized cutoffs offer a balanced, cost-efficient default, particularly in CKD and anemia, while a double cutoff retains advantages in obesity.

Plasma phosphorylated p-tau 217 levels vary with biological factors such as kidney dysfunction, body mass index (BMI), and anemia. It remains unclear whether a biological subgroup–specific optimal cutoff or a double-cutoff strategy could enhance diagnostic accuracy and cost efficiency beyond the standard single cutoff.

To compare the diagnostic and economic performance of 3 plasma p-tau217 classification strategies for detecting amyloid-β (Aβ) positivity: standard single cutoff, subgroup-specific optimal cutoff, and double cutoff.

This cohort study was a multicenter cross-sectional study conducted from 2016 to 2023; analyses were completed in 2025. Participants were recruited from multiple memory clinics and community-based cohorts. All participants had amyloid positron emission tomography (PET) imaging, clinical evaluation, and p-tau217 testing with measures of estimated glomerular filtration rate (eGFR), BMI, and hemoglobin. Measurements of p-tau217 were made using UGOT Simoa and Roche Elecsys, and the %p-tau217 ratio was assessed using a tau multianalyte assay (C2N Diagnostics LLC).

Kidney function (chronic kidney disease [CKD], eGFR <60 mL/min/1.73 m2; advanced CKD, eGFR <45 mL/min/1.73 m2), underweight (BMI <18.5), obesity (BMI ≥27.5), and anemia (hemoglobin <12 g/dL in women, <13 g/dL in men).

Plasma p-tau217 concentration; standard single cutoff, optimal cutoffs, and double cutoff for Aβ positivity (Centiloid ≥25.5); accuracy; and cost-effectiveness estimated from false-positive, false-negative, and confirmatory imaging costs.

A total of 2571 participants were analyzed with UGOT, 1578 with Roche, and 304 with the C2N %p-tau217 ratio. The mean (SD) age was similar across cohorts (71.3 [8.6] years in the UGOT cohort, 71.3 [8.5] years in the Roche cohort, and 71.8 [7.8] years in the C2N cohort); there were 1633 (63.5%), 1006 (63.8%), and 191 (62.8%) women and 938 (36.5%), 572 (36.2%), and 113 (37.2%) men, respectively. In the UGOT cohort, the optimal cutoff improved diagnostic accuracy compared with the standard single cutoff, particularly in CKD and anemia (CKD: from 0.65; 95% CI, 0.57-0.72; to 0.83; 95% CI, 0.76-0.89; anemia: from 0.80; 95% CI, 0.76-0.84; to 0.86; 95% CI, 0.82-0.90), with consistent findings in the Roche cohort. In all biological subgroups, the double-cutoff strategy also increased accuracy relative to the single cutoff and reduced false classifications but yielded 12% to 39% intermediate results. When compared directly, the optimal cutoff provided higher accuracy than the double cutoff for CKD while lowering total diagnostic costs. For anemia, the double cutoff showed slightly higher accuracy but required confirmatory PET in up to 25% of cases, offsetting its economic advantage. In obesity, the double cutoff remained superior for both diagnostic accuracy and cost efficiency.

This study found that both the optimal cutoff and the double-cutoff strategy outperformed the standard single cutoff, each showing distinct strengths across subgroups. These findings support biologically informed thresholds to improve diagnostic accuracy and cost efficiency when implementing plasma p-tau217.