ArticlePloS one2018
Protein variability in cerebrospinal fluid and its possible implications for neurological protein biomarker research.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Differential DNA methylation in blood as potential mediator of the association between ambient PMMolecular psychiatry · 2026Article
- Cerebrospinal fluid biomarkers reveal transdiagnostic synaptic dysfunction across major psychiatric disorders.Nature communications · 2026Article
- Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME/CFS.Scientific reports · 2026Article
- ProteoGyver: a fast, user-friendly tool for routine QC and analysis of MS-based proteomics data.Bioinformatics (Oxford, England) · 2026Article
- Cerebrospinal Fluid-Derived Extracellular Vesicles: A Proteomic and Transcriptomic Comparative Analysis of Enrichment Protocols.Journal of extracellular biology · 2025Article
- Review
- Binding of Pro-Inflammatory Proteins S100A8 or S100A9 to Amyloid-β Peptide Suppresses Its Fibrillation.Biomolecules · 2025Article
- Temporal phosphoproteomics reveals circuitry of phased propagation in insulin signaling.Nature communications · 2025Article
- Addressing inter individual variability in CSF levels of brain derived proteins across neurodegenerative diseases.Scientific reports · 2025Article
- Extracellular Histones Profiles of Pediatric H3K27-Altered Diffuse Midline Glioma.Molecular diagnosis & therapy · 2025Article
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Clinical importance of cerebrospinal fluid protein levels in HIV-associated cryptococcal meningitis: Insights from a prospective cohort study in Uganda.Medical mycology · 2024Article
- Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Central nervous system-derived extracellular vesicles: the next generation of neural circulating biomarkers?Translational neurodegeneration · 2024Review
- Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.medRxiv : the preprint server for health sciences · 2024Article
- CSF protein ratios with enhanced potential to reflect Alzheimer's disease pathology and neurodegeneration.Molecular neurodegeneration · 2024Article
- Utility of Cerebrospinal Fluid Protein Levels as a Potential Predictive Biomarker of Disease Severity in HIV-Associated Cryptococcal Meningitis.medRxiv : the preprint server for health sciences · 2023Article
- An LC-ESI-MS/MS method for determination of ondansetron in low-volume plasma and cerebrospinal fluid: Method development, validation, and clinical application.Journal of pharmaceutical and biomedical analysis · 2023Article
- Investigation of Inter- and Intra-Day Variability of Tear Fluid Regarding Flow Rate, Protein Concentration as well as Protein Composition.Investigative ophthalmology & visual science · 2023Article
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Authors and funding
11 authors.
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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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