# Double cutoff strategies for plasma pTau217 to predict Tau PET positivity across multiple assay platforms: Tau-enriched and Tau-scarce cohorts for cost-effective clinical use

## TL;DR

This study compares single and double cutoff strategies for plasma pTau217 to predict tau PET positivity, aiming to improve accuracy and reduce costs in clinical settings.

## Contribution

The study introduces and evaluates double cutoff strategies for pTau217 across multiple assay platforms to enhance clinical utility.

## Key findings

- Single cutoffs showed good accuracy (AUCs > 0.80) across most assays except for C2N ratio.
- Double cutoffs modestly improved accuracy but increased intermediate groups in the tau-scarce cohort.
- Cost analyses revealed reductions in most settings but increases for Lilly-MSD and Janssen-Simoa.

## Abstract

We aimed to evaluate whether double cutoff strategies for plasma pTau217 across multiple assay platforms improve tau PET positivity prediction compared with single cutoffs and support cost-effective clinical use.

We analyzed two cohorts: K-ROAD (n = 120; tau-enriched) and NA-ADNI (n = 280; tau-scarce). Tau PET positivity was defined within the temporal meta-ROI as SUVR > mean + 2 SD of Aβ-negative CU. Single and double cutoffs were compared for accuracy and misclassification-related costs.

Single cutoffs showed good accuracy across most assays (AUCs > 0.80), except for C2N ratio. Double cutoffs modestly improved accuracy but expanded intermediate groups, in the tau-scarce cohort. Cost analyses revealed assay- and cohort-specific effects, with reductions in most settings but increases for Lilly-MSD and Janssen-Simoa.

Double cutoff strategies should be applied with attention to assay platform and cohort context. Accuracy gains were modest, but clinical utility lies in reducing misclassification costs and guiding confirmatory PET use.

The online version contains supplementary material available at 10.1186/s13195-025-01952-y.