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Cited by 75Advanced Proteomics Techniques and ApplicationsClinical Laboratory Practices and Quality ControlCerebrospinal fluid and hydrocephalus

Protein variability in cerebrospinal fluid and its possible implications for neurological protein biomarker research

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Schilde, Lukas M., Kösters, Steffen, Steinbach, Simone, Schork, Karin, Eisenacher, Martin, Galozzi, Sara, Turewicz, Michael, Barkovits, Katalin +3 more·2018·PLOS ONE
DOI 10.1371/journal.pone.0206478PMC PMC6264484
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Abstract

Cerebrospinal fluid is investigated in biomarker studies for various neurological disorders of the central nervous system due to its proximity to the brain. Currently, only a limited number of biomarkers have been validated in independent studies. The high variability in the protein composition and protein abundance of cerebrospinal fluid between as well as within individuals might be an important reason for this phenomenon. To evaluate this possibility, we investigated the inter- and intraindividual variability in the cerebrospinal fluid proteome globally, with a specific focus on disease biomarkers described in the literature. Cerebrospinal fluid from a longitudinal study group including 12 healthy control subjects was analyzed by label-free quantification (LFQ) via LC-MS/MS. Data were quantified via MaxQuant. Then, the intra- and interindividual variability and the reference change value were calculated for every protein. We identified and quantified 791 proteins, and 216 of these proteins were abundant in all samples and were selected for further analysis. For these proteins, we found an interindividual coefficient of variation of up to 101.5% and an intraindividual coefficient of variation of up to 29.3%. Remarkably, these values were comparably high for both proteins that were published as disease biomarkers and other proteins. Our results support the hypothesis that natural variability greatly impacts cerebrospinal fluid protein biomarkers because high variability can lead to unreliable results. Thus, we suggest controlling the variability of each protein to distinguish between good and bad biomarker candidates, e.g., by utilizing reference change values to improve the process of evaluating potential biomarkers in future studies.

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  • CSF offers an attractive alternative to plasma when studying the CNS because many CSF proteins are relevant to CNS diseases.

    “CSF offers an attractive alternative to plasma when studying the central nervous system (CNS) because many CSF proteins are relevant to CNS diseases (14).”

    From Low overlap of plasma and CSF protein quantitative trait loci affects protein discovery for neurological disease (2026) · cites this paper as [14]

    The Introduction says some CSF proteins originate in the CNS and that CSF has been investigated for biomarkers of neurological disease. It supports CSF’s relevance to CNS research, but does not describe CSF as an attractive alternative to plasma; its accessibility comparison is with brain biopsy. (LLM, conf=0.83)

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Authors
Schilde, L. M., Kösters, S., Steinbach, S., Schork, K., Eisenacher, M., Galozzi, S., Turewicz, M., Barkovits, K., Mollenhauer, B., Marcus, K., & May, C.
Affiliations
  • Ruhr University Bochum (DE)
  • Universitätsmedizin Göttingen (DE)
Corresponding author
Marcus, Katrin
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2018-11-29
Volume
13
Issue
11
Pages
e0206478
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0206478
PMC
PMC6264484
OpenAlex
W2903178772
Cited by
75
References
1
Citations by year
2026: 8 · 2025: 14 · 2024: 13 · 2023: 10 · 2022: 10 · 2021: 3 · 2020: 14 · 2019: 1 · 2018: 1 · 2017: 1
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dokumentenrepositorium der RUB (Ruhr University Bochum) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Deutsche Parkinson Gesellschaft
  • The HUPO Brain Proteome Project
  • PURE, a project of Northrhine Westfalia a federal German state
  • Bundesministerium für Bildung und Forschung (FKZ 031 A 534A, FKZ 01DN14023)
  • Medical Faculty Ruhr-University Bochum (FoRUM)
  • Horizon 2020 (NISCI) (681094)
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
cerebrospinal fluid proteome, protein variation, interindividual variability, within-person variability, reference change value, biomarker validation, coefficient of variation, label-free quantification
MeSH terms
Adult, Aged, Aged, 80 and over, Cerebrospinal Fluid Proteins, Female, Humans, Longitudinal Studies, Male, Middle Aged, Nervous System Diseases, Biomarkers, Proteomics, Healthy Volunteers

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