학술논문
Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology
Document Type
Author
Therriault, Joseph; Woo, Marcel S.; Salvadó, Gemma; Gobom, Johan; Karikari, Thomas; Janelidze, Shorena; Servaes, Stijn; Rahmouni, Nesrine; Tissot, Cécile; Ashton, Nicholas J.; Lessa Benedet, Andréa; Montoliu-Gaya, Laia; Macedo, Arthur C.; Lussier, Firoza Z.; Stevenson, Jenna; Vitali, Paolo; Friese, Manuel A.; Massarweh, Gassan; Soucy, Jean Paul; Pascoal, Tharick A.; Stomrud, Erik; Palmqvist, Sebastian; Mattsson-Carlgren, Niklas; Gauthier, Serge; Zetterberg, Henrik, 1973; Hansson, Oskar; Blennow, Kaj, 1958; Rosa-Neto, Pedro
Source
Molecular Neurodegeneration. 19(1)
Subject
Language
English
ISSN
1750-1326
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.