Performance of Elecsys pTau217 plasma immunoassay to detect brain amyloid pathology

INTRODUCTIONWe evaluated clinical performance of the fully-automated, high-throughput, prototype Elecsys(R) Phospho-Tau (217P) plasma immunoassay (Roche Diagnostics) for detecting amyloid pathology. METHODSPlasma 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. RESULTSFor 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. DISCUSSIONThe pTau217 plasma immunoassay accurately detects amyloid pathology, irrespective of cognitive status. RESEARCH IN CONTEXTO_ST_ABS1. Systematic reviewC_ST_ABSPrior 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 Alzheimers disease (AD) diagnosis, showing high concordance with amyloid positron emission tomography (PET) and cerebrospinal fluid biomarkers. 2. InterpretationThe high-throughput, fully automated Elecsys(R) 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 ([&ge;] 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 directionsThese 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. HighlightsO_LIEvaluated Elecsys(R) pTau217 plasma immunoassay (Roche Diagnostics) in five cohorts. C_LIO_LIHigh performance detecting amyloid pathology in cognitively impaired/unimpaired. C_LIO_LIHigh negative predictive value supported utility as a pre-screener in AD. C_LIO_LIIdentified cutoffs suitable as rule out pre-screener tools in clinical trials. C_LIO_LIReinforced use of high-throughput pTau217 plasma measurements to aid AD diagnosis. C_LI 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