Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology

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. PascoalErik Stomrud, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Serge Gauthier, Henrik Zetterberg, Oskar Hansson, Kaj Blennow, Pedro Rosa-Neto

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

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.

Originalspråkengelska
Artikelnummer2
TidskriftMolecular Neurodegeneration
Volym19
Nummer1
DOI
StatusPublished - 2024

Ämnesklassifikation (UKÄ)

  • Neurovetenskaper

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