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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 LU ; Gobom, Johan ; Karikari, Thomas K. ; Janelidze, Shorena LU ; Servaes, Stijn ; Rahmouni, Nesrine ; Tissot, Cécile and Ashton, Nicholas J. , et al. (2024) In Molecular Neurodegeneration 19(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Neurodegeneration
volume
19
issue
1
article number
2
publisher
BioMed Central (BMC)
external identifiers
  • pmid:38185677
  • scopus:85181942333
ISSN
1750-1326
DOI
10.1186/s13024-023-00689-2
language
English
LU publication?
yes
id
96bc426b-d9cd-4684-95ca-9eb427ab0ab2
date added to LUP
2024-02-07 11:48:39
date last changed
2024-04-23 19:22:29
@article{96bc426b-d9cd-4684-95ca-9eb427ab0ab2,
  abstract     = {{<p>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-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub> with established immunoassay techniques. Methods: We measured p-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub> 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-tau<sub>181</sub>, p-tau<sub>217</sub> and p-tau<sub>231</sub>. 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-tau<sub>217</sub> were highly comparable in terms of diagnostic performance, between-group effect sizes and associations with PET biomarkers. In contrast, p-tau<sub>181</sub> and p-tau<sub>231</sub> 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.</p>}},
  author       = {{Therriault, Joseph and Woo, Marcel S. and Salvadó, Gemma and Gobom, Johan and Karikari, Thomas K. and Janelidze, Shorena and Servaes, Stijn and Rahmouni, Nesrine and Tissot, Cécile and Ashton, Nicholas J. and Benedet, Andréa Lessa and Montoliu-Gaya, Laia and Macedo, Arthur C. and Lussier, Firoza Z. and Stevenson, Jenna and Vitali, Paolo and Friese, Manuel A. and Massarweh, Gassan and Soucy, Jean Paul and Pascoal, Tharick A. and Stomrud, Erik and Palmqvist, Sebastian and Mattsson-Carlgren, Niklas and Gauthier, Serge and Zetterberg, Henrik and Hansson, Oskar and Blennow, Kaj and Rosa-Neto, Pedro}},
  issn         = {{1750-1326}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Molecular Neurodegeneration}},
  title        = {{Comparison of immunoassay- with mass spectrometry-derived p-tau quantification for the detection of Alzheimer’s disease pathology}},
  url          = {{http://dx.doi.org/10.1186/s13024-023-00689-2}},
  doi          = {{10.1186/s13024-023-00689-2}},
  volume       = {{19}},
  year         = {{2024}},
}