Biomarkers.

Area of Science:

• Neurology
• Biochemistry
• Medical Diagnostics

Background:

• Evaluating the clinical performance of a novel, automated Elecsys® Phospho-Tau (217P) Plasma immunoassay for amyloid pathology detection.
• Assessing the discriminative ability of plasma phosphorylated tau 217 (pTau217) against amyloid PET visual read and centiloid classifications in a real-world cohort.

Purpose of the Study:

• To determine the accuracy of the prototype pTau217 plasma immunoassay in detecting amyloid pathology.
• To compare the performance of pTau217 with established methods like amyloid PET visual read and centiloid classifications.
• To evaluate the potential of this assay for implementation in routine clinical practice.

Main Methods:

• Prospective, multicenter study involving 603 adults aged 55-80 with cognitive impairment.
• Collection of EDTA plasma samples from patients undergoing evaluation for Alzheimer's disease or other cognitive decline causes.
• Measurement of plasma pTau217 concentrations using the prototype immunoassay and analysis using receiver operating characteristic curve analysis against PET visual read and centiloid classifications.

Main Results:

• The pTau217 plasma immunoassay demonstrated high accuracy with an AUC of 0.917 compared to PET visual read.
• Performance against centiloid classifications yielded AUCs between 0.896-0.925, influenced by chosen cut-offs.
• The study cohort was heterogeneous, reflecting routine clinical practice across primary and secondary care settings.

Conclusions:

• The prototype pTau217 plasma immunoassay accurately detects amyloid positivity in a diverse, real-world patient population with cognitive decline.
• The assay's automation and high-throughput nature support its potential integration into routine clinical diagnostics.
• Consideration of centiloid cut-off influences is recommended for future assessments using centiloid classifications.