Journal Article

DZNE-2026-01050

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Evaluation of a fully automated assay for the measurement of plasma pTau217 and a composite score integrating the ratio Aβ1-42/1-40 as biomarkers of Alzheimer's disease.

Morgado, B.Extern* ; Klafki, H.-W. ; Bauer, C. ; Steiert, A. ; Waniek, K. ; Lachmann, I. ; Osterloh, D. ; Esselmann, H. ; Hansen, N. ; Schuchhardt, J. ; Wiltfang, J. (Last author)DZNE*

2026
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00406-025-02123-8

Abstract: Plasma phosphorylated Tau217 (pTau217) represents a sensitive blood-based biomarker for Alzheimer’s disease (AD). This study investigated the performance of plasma pTau217 alone and as a composite score (Aβ1-40/Aβ1-42*pTau217) for detecting low Aβ1-42/1-40 in cerebrospinal fluid (CSF) as a surrogate marker of brain β-amyloid pathological changes.We analysed plasma samples from 82 pre-selected participants who were dichotomized according to their CSF Aβ42/40 ratio after data-driven cutoff determination by Gaussian mixture modelling. The study cohort included patients in very early disease stages with mild cognitive impairment (MCI) due to AD and mild dementia due to AD in the Aβ-positive group and MCI due to other causes and mild dementia due to other causes in the Aβ-negative group. Concentrations of plasma pTau181 and pTau217 were determined on the fully automated LUMIPULSE platform. Additionally, plasma Aβ1-42/1-40 and pTau217 were assessed after consecutive Aβ- and Tau-immunoprecipitations (IPs). Corrections for age and sex effects in primary variables were done using a multivariate linear model on a logarithmic scale. Results are reported using both adjusted and unadjusted values.After adjustment for age and sex, median plasma pTau217 was increased by 203% in participants with low CSF Aβ1-42/1-40 (i.e. Aβ-positive), while pTau181 was increased by only 61%. PTau217 showed a larger area under the receiver operating characteristics curve (AUC) of 0.88 in identifying Aβ-positive individuals compared to plasma pTau181 (AUC: 0.78). Plasma Aβ1-42/1-40 ratio in Aβ-IP eluates (adjusted for age and sex) was decreased by only 10%, and the standardized effect size (Cohen´s d) was smaller than that of pTau217. Tau-IP did not improve the performance of the pTau217 assay (p = 0.568, DeLong test). However, the Aβ1-40/Aβ1-42*pTau217 ratio following immunoprecipitations appeared to outperform the single blood biomarkers.PTau217 as measured with the fully automated Lumipulse G pTau217 Plasma < RUO > assay demonstrated high accuracy for detecting low CSF Aβ1-42/1-40 and appears to represent a particularly attractive biomarker for future implementation in clinical practice. Furthermore, the composite score Aβ1-40/Aβ1-42*pTau217 showed promise for enhancing the blood-based early and differential diagnosis of AD.The online version contains supplementary material available at 10.1007/s00406-025-02123-8.

Keyword(s): Alzheimer’s disease ; Aβ1-40/Aβ1-42*pTau217 composite marker ; Blood-based biomarker ; Pre-analytical immunoprecipitation ; pTau181 ; pTau217

Note: ISSN 1433-8491 not unique: **2 hits**.

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Contributing Institute(s):

1. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; SCOPUS

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