METHODS article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1568971
Analytical and Clinical Validation of a High Accuracy Fully Automated Digital Immunoassay for Plasma Phospho-Tau 217 for Clinical Use in Detecting Amyloid Pathology
Provisionally accepted
David Wilson1*
Meenakshi Khare1Gallen Triana-Baltzer2Michele Wolfe1Patrick Sheehy1Karen Copeland3Lyndal Hesterberg4Ann Vasko1Wiesje M van der Flier5
Inge Maria Wilhelmina Verberk5
Charlotte Elisabeth Teunissen5Mike Miller1- 1Quanterix Corporation, Billerica, United States
- 2Johnson and Johnson Innovative Medicine, La Jolla, CA, United States
- 33Boulder Statistics, Steamboat Springs, CO, United States
- 4HCS Control Systems, Denver, CO, United States
- 5Department of Laboratory Medicine, Amsterdam UMC, Amsterdam, Netherlands
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Background: With the emergence of disease-modifying therapies for Alzheimer's disease (AD), there is an urgent need for scalable, accurate, and well-validated blood test alternatives to positron emission topography (PET) and lumbar punctures for identifying amyloid pathology to facilitate identification of candidates for therapy. Plasma p-Tau 217 has emerged as a plasma-based biomarker with sufficient sensitivity and specificity to both rule out and rule in amyloid pathology with high confidence, potentially serving as a readily scalable non-invasive test to aid AD diagnosis. In this report, we describe robust analytical and clinical validation of a lab developed test for plasma p-Tau 217 suitable for clinical diagnostic use.A high sensitivity digital immunoassay using single molecule array (Simoa) technology was developed for plasma p-Tau 217 utilizing a 2-cutoff approach. The assay was analytically validated with industry standard protocols and clinically validated across 873 symptomatic individuals from two independent clinical cohorts using PET or cerebrospinal fluid (CSF) biomarkers as comparators.The assay exhibited acceptable analytical characteristics with aan analytical sensitivity enabling measurement of plasma p-Tau 217 in all clinical samples. Excluding results between the two cutoffs, clinical sensitivity, specificity, and agreement with comparator methods (accuracy) were >90%, with 30.9% of the samples falling in the intermediate zone between the two cutoffs.Discussion: The performance characteristics of the Simoa p-Tau 217 assay align with current accuracy recommendations for blood-based biomarker test performance for diagnostic use, making the test suitable for clinical use under the Clinical Laboratory Improvement Act (CLIA) as a diagnostic plasma test to aid in Alzheimer's diagnosis.
Keywords: Alzheimer's disease1, immumoassay2, p-Tau 2173, validation4, amyloid5, SiMoA6
Received: 31 Jan 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Wilson, Khare, Triana-Baltzer, Wolfe, Sheehy, Copeland, Hesterberg, Vasko, van der Flier, Verberk, Teunissen and Miller. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: David Wilson, Quanterix Corporation, Billerica, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.