Elecsys pTau217 plasma immunoassay detection of amyloid pathology in clinical cohorts

Abstract

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

Methods: Plasma tau phosphorylated at threonine 217 (pTau217) levels were determined in samples from cognitively impaired and unimpaired individuals from five cohorts (N = 2148) 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+) individuals 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 the curve was 0.878 (95% confidence interval [CI] 0.840, 0.915; impaired) and 0.907 (95% CI 0.885, 0.929; unimpaired). A 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.

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 HIGHLIGHTS: The Elecsys^® pTau217 plasma immunoassay (Roche Diagnostics) was evaluated across five cohorts. The pTau217 plasma immunoassay demonstrated high performance in detecting amyloid pathology in both cognitively impaired and unimpaired individuals. The pTau217 plasma immunoassay had a high negative predictive value which supports its utility as a pre-screening tool for Alzheimer's disease (AD). The pTau217 plasma immunoassay cutoffs identified are suitable for use as rule-out pre-screener tools in clinical trials. These findings reinforce the value of the high-throughput pTau217 plasma immunoassay measurements to aid AD diagnosis.

Keywords: Alzheimer's disease; amyloid pathology; blood‐based biomarkers; cognitive decline; dementia; immunoassay; plasma; plasma tau phosphorylated at threonine 217; pre‐screening; secondary prevention.