Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer's disease pathology
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Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer's disease pathology. / 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; Pascoal, Tharick A; Stomrud, Erik; Palmqvist, Sebastian; Mattsson-Carlgren, Niklas; Gauthier, Serge; Zetterberg, Henrik; Hansson, Oskar; Blennow, Kaj; Rosa-Neto, Pedro.
in: MOL NEURODEGENER, Jahrgang 19, Nr. 1, 07.01.2024, S. 2.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer's disease pathology
AU - Therriault, Joseph
AU - Woo, Marcel S
AU - Salvadó, Gemma
AU - Gobom, Johan
AU - Karikari, Thomas K
AU - Janelidze, Shorena
AU - Servaes, Stijn
AU - Rahmouni, Nesrine
AU - Tissot, Cécile
AU - Ashton, Nicholas J
AU - Benedet, Andréa Lessa
AU - Montoliu-Gaya, Laia
AU - Macedo, Arthur C
AU - Lussier, Firoza Z
AU - Stevenson, Jenna
AU - Vitali, Paolo
AU - Friese, Manuel A
AU - Massarweh, Gassan
AU - Soucy, Jean-Paul
AU - Pascoal, Tharick A
AU - Stomrud, Erik
AU - Palmqvist, Sebastian
AU - Mattsson-Carlgren, Niklas
AU - Gauthier, Serge
AU - Zetterberg, Henrik
AU - Hansson, Oskar
AU - Blennow, Kaj
AU - Rosa-Neto, Pedro
N1 - © 2023. The Author(s).
PY - 2024/1/7
Y1 - 2024/1/7
N2 - 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.
AB - 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.
U2 - 10.1186/s13024-023-00689-2
DO - 10.1186/s13024-023-00689-2
M3 - SCORING: Journal article
C2 - 38185677
VL - 19
SP - 2
JO - MOL NEURODEGENER
JF - MOL NEURODEGENER
SN - 1750-1326
IS - 1
ER -
