Cited by 123Alzheimer's disease research and treatmentsAdvanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and Applications

Tau Protein Quantification in Human Cerebrospinal Fluid by Targeted Mass Spectrometry at High Sequence Coverage Provides Insights into Its Primary Structure Heterogeneity

Barthélemy, Nicolas R, Fenaille, François, Hirtz, Christophe, Sergeant, Nicolas, Schraen-Maschke, Susanna, Vialaret, Jérôme, Buée, Luc, Gabelle, Audrey +3 more·2016·Journal of Proteome Research

Abstract

Tau protein plays a major role in neurodegenerative disorders, appears to be a central biomarker of neuronal injury in cerebrospinal fluid (CSF), and is a promising target for Alzheimer's disease immunotherapies. To quantify tau at high sensitivity and gain insights into its naturally occurring structural variations in human CSF, we coupled absolute quantification using protein standard with the multiplex detection capability of targeted high-resolution mass spectrometry (MS) on a Quadrupole-Orbitrap instrument. Using recombinant tau we developed a step-by-step workflow optimization including an extraction protocol that avoided affinity reagents and achieved the monitoring of 22 tau peptides uniformly distributed along the tau sequence. The lower limits of quantification ranged (LLOQ) from 150 to 1500 pg/mL depending on the peptide. Applied to endogenous CSF tau, up to 19 peptides were detected. Interestingly, there were significant differences in the abundance of peptides depending on their position in the sequence, with peptides from the tau mid-domain appearing significantly more abundant than peptides from the N- and C-terminus domains. This MS-based strategy provided results complementary to those of previous ELISA or Western Blot studies of CSF tau and could be applied to tau monitoring in human CSF cohorts.

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Crossref · 10.1021/acs.jproteome.5b01001

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  • Mass spectroscopy studies indicate that CSF tau predominantly consists of tau fragments spanning amino acids 150-250 of the tau protein, with the amino and carboxyl termini presumably having been digested.

    “In addition, mass spectroscopy studies indicate that CSF tau predominantly consists of tau fragments spanning amino acids 150–250 of the tau protein, with the amino and carboxyl termini presumably having been digested264,265.”

    From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [265]

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Authors
Barthélemy, N. R., Fenaille, F., Hirtz, C., Sergeant, N., Schraen-Maschke, S., Vialaret, J., Buée, L., Gabelle, A., Junot, C., Lehmann, S., & Becher, F.
Affiliations
  • Inserm (FR)
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
  • Inserm, UMR-S 1172, Alzheimer & Tauopathies, Centre de Recherche Jean-Pierre Aubert, Lille, Univ. Lille, Faculté de Médecine, Lille F-59045, France
  • CEA, iBiTec-S, Service de Pharmacologie et d’Immunoanalyse, Laboratoire d’Etude du Métabolisme des Médicaments, Gif-sur-Yvette 91191, France
Corresponding author
Barthélemy, Nicolas R
Venue
Journal of Proteome Research
Published
2016-01-19
Volume
15
Issue
2
Pages
667-676
ISSN
  • 1535-3893 (ISSN-L)
  • 1535-3907
OpenAlex
W2222784460
Cited by
123
References
43
Citations by year
2026: 3 · 2025: 7 · 2024: 15 · 2023: 8 · 2022: 8 · 2021: 19 · 2020: 18 · 2019: 13 · 2018: 17 · 2017: 12 · 2016: 3
FWCI
12.06
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Proteome Research (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
Keywords
tau protein, cerebrospinal fluid, absolute quantification, targeted mass spectrometry, peptide sequence coverage, neurodegenerative diseases, Alzheimer's disease biomarkers
MeSH terms
Amino Acid Sequence, Chromatography, Liquid, Humans, Molecular Sequence Data, Peptides, Mass Spectrometry, Reproducibility of Results, Biomarkers, tau Proteins

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