Published in:
Open Access
01-12-2024 | Alzheimer's Disease | Research article
Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology
Authors:
Joseph Therriault, Marcel S. Woo, Gemma Salvadó, Johan Gobom, Thomas K. Karikari, Shorena Janelidze, Stijn Servaes, Nesrine Rahmouni, Cécile Tissot, Nicholas J. Ashton, Andréa Lessa Benedet, Laia Montoliu-Gaya, Arthur C. Macedo, Firoza Z. Lussier, Jenna Stevenson, Paolo Vitali, Manuel A. Friese, Gassan Massarweh, Jean-Paul Soucy, Tharick A. Pascoal, Erik Stomrud, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Serge Gauthier, Henrik Zetterberg, Oskar Hansson, Kaj Blennow, Pedro Rosa-Neto
Published in:
Molecular Neurodegeneration
|
Issue 1/2024
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Abstract
Background
Antibody-based immunoassays have enabled quantification of very low concentrations of phosphorylated tau (p-tau) protein forms in cerebrospinal fluid (CSF), aiding in the diagnosis of AD. Mass spectrometry enables absolute quantification of multiple p-tau variants within a single run. The goal of this study was to compare the performance of mass spectrometry assessments of p-tau181, p-tau217 and p-tau231 with established immunoassay techniques.
Methods
We measured p-tau181, p-tau217 and p-tau231 concentrations in CSF from 173 participants from the TRIAD cohort and 394 participants from the BioFINDER-2 cohort using both mass spectrometry and immunoassay methods. All subjects were clinically evaluated by dementia specialists and had amyloid-PET and tau-PET assessments. Bland–Altman analyses evaluated the agreement between immunoassay and mass spectrometry p-tau181, p-tau217 and p-tau231. P-tau associations with amyloid-PET and tau-PET uptake were also compared. Receiver Operating Characteristic (ROC) analyses compared the performance of mass spectrometry and immunoassays p-tau concentrations to identify amyloid-PET positivity.
Results
Mass spectrometry and immunoassays of p-tau217 were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau181 and p-tau231 concentrations measured using antibody-free mass spectrometry had lower performance compared with immunoassays.
Conclusions
Our results suggest that while similar overall, immunoassay-based p-tau biomarkers are slightly superior to antibody-free mass spectrometry-based p-tau biomarkers. Future work is needed to determine whether the potential to evaluate multiple biomarkers within a single run offsets the slightly lower performance of antibody-free mass spectrometry-based p-tau quantification.