Performance of Elecsys pTau217 plasma immunoassay to detect brain amyloid pathology

  1. Derrek P. Hibar
  2. Alina Bauer
  3. Christina Rabe
  4. Niels Borlinghaus
  5. Alexander Jethwa
  6. Gwendlyn Kollmorgen
  7. Annunziata Di Domenico
  8. Henrik Zetterberg
  9. Kaj Blennow
  10. Colin L. Masters
  11. Reisa A. Sperling
  12. Tobias Bittner
Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

Abstract

INTRODUCTION

We evaluated clinical performance of the fully-automated, high-throughput, prototype Elecsys ® Phospho-Tau (217P) plasma immunoassay (Roche Diagnostics) for detecting amyloid pathology.

METHODS

Plasma pTau217 levels were determined in samples from cognitively impaired and unimpaired individuals from five cohorts ( N =7252) using the pTau217 plasma immunoassay. Clinical performance was evaluated against amyloid positron emission tomography.

RESULTS

For cognitively impaired, mean plasma pTau217 levels for amyloid-positive (A+) were higher ( n =394; 0.835 pg/mL) than amyloid-negative (A–) individuals ( n =144; 0.361 pg/mL); similarly, for cognitively unimpaired, A+ ( n =224; 0.516 pg/mL) and A– individuals ( n =1386; 0.220 pg/mL). Area under curve was 0.878 (95% confidence interval [CI] 0.840, 0.915) (impaired) and 0.907 (95% CI 0.885, 0.929) (unimpaired). Cutoff < 0.189 pg/mL reliably ruled-out individuals without amyloid pathology. High negative predictive values [92.51% (impaired); 98.60% (unimpaired)] were observed with sensitivity/specificity of 98.98%/29.17% and 95.54%/50.72%, respectively.

DISCUSSION

The pTau217 plasma immunoassay accurately detects amyloid pathology, irrespective of cognitive status.

RESEARCH IN CONTEXT

1. Systematic review

Prior literature on blood-based biomarkers, particularly pTau217, was reviewed using PubMed and recent conference proceedings. Several studies support plasma pTau217 as a promising biomarker to aid Alzheimer’s disease (AD) diagnosis, showing high concordance with amyloid positron emission tomography (PET) and cerebrospinal fluid biomarkers.

2. Interpretation

The high-throughput, fully automated Elecsys ® prototype pTau217 plasma immunoassay (Roche Diagnostics Ltd) accurately detected amyloid pathology across cognitively diverse populations in a large multi-cohort study ( N =7252). The assay achieved a high area under curve (≥ 0.878) with respect to amyloid PET. A low-risk cutoff (< 0.189 pg/mL) showed good negative predictive value, supporting utility as a rule out tool.

3. Future directions

These results confirm the pTau217 plasma immunoassay as a reliable, scalable, and clinically useful biomarker for detection of amyloid pathology. Prospective validation in diverse populations and evaluation of outcomes in early AD care pathways are essential.

Highlights

  • Evaluated Elecsys ® pTau217 plasma immunoassay (Roche Diagnostics) in five cohorts.

  • High performance detecting amyloid pathology in cognitively impaired/unimpaired.

  • High negative predictive value supported utility as a pre-screener in AD.

  • Identified cutoffs suitable as rule out pre-screener tools in clinical trials.

  • Reinforced use of high-throughput pTau217 plasma measurements to aid AD diagnosis.

Trial registration number: A4, NCT02008357 ; SKYLINE, NCT05256134 ; AIBL, SAGE Project ID Number: 2022/PID06188; SVHM Local Ref ID: HREC 028/06; CREAD, NCT02670083 ; CREAD2, NCT03114657

Article activity feed

  1. Version published to 10.1101/2025.08.08.25333024 on medRxiv