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

  • Joseph Therriault (Geteilte/r Erstautor/in)
  • Marcel S Woo (Geteilte/r Erstautor/in)
  • Gemma Salvadó (Geteilte/r Erstautor/in)
  • 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


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.

Bibliografische Daten

StatusVeröffentlicht - 07.01.2024

Anmerkungen des Dekanats

© 2023. The Author(s).

PubMed 38185677