A Parallel Reaction Monitoring Mass Spectrometric Method for Analysis of Potential CSF Biomarkers for Alzheimer's Disease
Open accessAbstract
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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Strong associations can be found between some synaptic proteins but not all, and synaptic biomarkers have been reported to lack correlation with CSF neurofilament light levels.
“The diversity of synaptic pathology across several neurodegenerative dementia is further reflected by the fact that strong associations can be found between some synaptic proteins but not all, as well as the reported lack of correlation of synaptic biomarkers with CSF neurofilament light (NfL) levels [1, 9–11].”
Recent studies in cerebrospinal fluid revealed altered NPTXs levels in several neurodegenerative disorders.
“Recent studies in cerebrospinal fluid (CSF) revealed altered NPTXs levels in several neurodegenerative disorders.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Brinkmalm et al. 2018
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Self-citationAn astrocyte-derived cytokine TIMP-1 restores synaptic plasticity in an Alzheimer’s disease modelPreprint
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Self-citation
- 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
- ORCID
- 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
- green
- discovery.ucl.ac.uk
- 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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