Cited by 111Advanced Proteomics Techniques and ApplicationsMass Spectrometry Techniques and ApplicationsAlzheimer's disease research and treatments

A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease

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Brinkmalm, Gunnar, Sjödin, Simon, Simonsen, Anja Hviid, Hasselbalch, Steen Gregers, Zetterberg, Henrik, Brinkmalm, Ann, Blennow, Kaj·2018·PROTEOMICS – Clinical Applications

Abstract

Scope: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM‐MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). Experimental design: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and two to three peptides per protein were quantified using stable isotope‐labeled peptide standards. Results: Coefficients of variation were generally below 15%. Clinical evaluation was performed on a cohort of 10 patients with Alzheimer's disease (AD) and 15 healthy subjects. Investigated proteins of the granin family exhibited the largest difference between the patient groups. Secretogranin‐2 (p<0.005) and neurosecretory protein VGF (p<0.001) concentrations were lowered in AD. For chromogranin A, two of three peptides had significantly lowered AD concentrations (p<0.01). The concentrations of the synaptic proteins neurexin‐1 and neuronal pentraxin‐1, as well as neurofascin were also significantly lowered in AD (p<0.05). The other investigated proteins, β2‐microglobulin, cystatin C, amyloid precursor protein, lysozyme C, neurexin‐2, neurexin‐3, and neurocan core protein, were not significantly altered. Conclusion and clinical relevance: PRM‐MS of protein panels is a valuable tool to evaluate biomarker candidates for neurodegenerative disorders.

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Authors
Brinkmalm, G., Sjödin, S., Simonsen, A. H., Hasselbalch, S. G., Zetterberg, H., Brinkmalm, A., & Blennow, K.
Affiliations
  • Sahlgrenska University Hospital (SE)
  • University of Copenhagen (DK)
Corresponding author
Brinkmalm, Gunnar
Venue
PROTEOMICS – Clinical Applications
Publisher
Wiley
Published
2017-11-23
Volume
12
Issue
1
ISSN
  • 1862-8346 (ISSN-L)
  • 1862-8354
OpenAlex
W2762397244
Cited by
111
References
83
Citations by year
2026: 1 · 2025: 3 · 2024: 6 · 2023: 10 · 2022: 16 · 2021: 24 · 2020: 27 · 2019: 15 · 2018: 9
FWCI
7.29
Type
journal article
Language
en
Open access
Locations
  • PROTEOMICS - CLINICAL APPLICATIONS (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Åhlén-stiftelsen
  • Stiftelsen för Gamla Tjänarinnor
  • H2020 European Research Council
  • Vetenskapsrådet
  • Magnus Bergvalls Stiftelse
  • Hjärnfonden
  • Torsten Söderbergs Stiftelse
  • Alzheimerfonden
  • Gun och Bertil Stohnes Stiftelse
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, cerebrospinal fluid biomarkers, protein biomarker panel, VGF, chromogranin A, synaptic proteins, NRXN1, neurofascin, neurodegenerative diseases
MeSH terms
Pentraxins, Aged, Alzheimer Disease, Amino Acid Sequence, C-Reactive Protein, Calcium-Binding Proteins, Chromatography, Liquid, Female, Humans, Male, Middle Aged, Nerve Growth Factors, Nerve Tissue Proteins, Peptide Fragments, Pilot Projects, Biomarkers, Cell Adhesion Molecules, Cell Adhesion Molecules, Neuronal, Gene Expression, Case-Control Studies, Neural Cell Adhesion Molecules, Proteomics, Chromogranin A, Secretogranin II, Tandem Mass Spectrometry, Proteolysis

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