1. Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer's disease pathology.
- Author
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Therriault, Joseph, Woo, Marcel S., Salvadó, Gemma, Gobom, Johan, Karikari, Thomas K., Janelidze, Shorena, Servaes, Stijn, Rahmouni, Nesrine, Tissot, Cécile, Ashton, Nicholas J., Benedet, Andréa Lessa, Montoliu-Gaya, Laia, Macedo, Arthur C., Lussier, Firoza Z., Stevenson, Jenna, Vitali, Paolo, Friese, Manuel A., Massarweh, Gassan, Soucy, Jean-Paul, and Pascoal, Tharick A.
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ALZHEIMER'S disease , *TAU proteins , *CHEMILUMINESCENCE immunoassay , *PATHOLOGY , *RECEIVER operating characteristic curves , *MASS spectrometry , *MASS transfer coefficients - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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