Development of a light-initiated chemiluminescence system for the detection of human plasma p-tau181

Abstract

Phosphorylated tau 181 (p-tau181) is a promising biomarker for predicting and monitoring Alzheimer’s disease (AD) neuropathology. However, existing commercial assays suffer from disadvantages such as high cost and insufficient detection sensitivity, limiting their clinical applications and suitability for routine laboratory use. In this study, we developed a novel light-initiated chemiluminescence assay (LiCA®) and evaluated its performance for quantifying plasma p-tau181 levels. A compact, fully automated LiCA® analyzer was developed for decentralized and point-of-care testing environments. Analytical performance of the p-tau181 assay on the analyzer was validated according to Clinical and Laboratory Standards Institute (CLSI) guidelines, with evaluation of precision, accuracy, linearity, detection capability, and interference. Reference intervals were established per EP28-A3c. Method comparison was conducted using Spearman’s correlation with the Simoa® pTau-181 Advantage V2.1 kit. The assay demonstrated excellent precision (coefficient of variation: 2.72–5.11%), high recovery accuracy (93.29–107.56%), and strong linearity (R = 0.9986) across a range of 0–200 pg/mL. Sensitivity parameters included limit of blank (LoB)=0.10 pg/mL, limit of detection (LoD)=0.19 pg/mL, limit of quantitation (LoQ)=0.30 pg/mL (20% CV) and LoQ=0.57 pg/mL (10% CV). Plasma p-tau181 was detectable in 100% of healthy individuals (n = 400), confirming the assay’s capability for baseline differentiation. Strong correlation with the Simoa® platform (ρ = 0.868) further validated clinical concordance. LiCA® offers a fully automated, random-access platform for highly sensitive and accurate measurement of p-tau181. It could be a viable tool for early screening and differential diagnosis of neurodegenerative diseases in both clinical trial settings and routine clinical practice.

Supplementary files

Article information

Article type
Paper
Submitted
28 May 2025
Accepted
17 Jul 2025
First published
18 Jul 2025

Analyst, 2025, Accepted Manuscript

Development of a light-initiated chemiluminescence system for the detection of human plasma p-tau181

Y. yang and X. Wang, Analyst, 2025, Accepted Manuscript , DOI: 10.1039/D5AN00590F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements