Identification of candidate cerebrospinal fluid biomarkers in parkinsonism using quantitative proteomics
Open accessAbstract
Introduction Neurodegenerative parkinsonian syndromes have significant clinical and pathological overlap, making early diagnosis difficult. Cerebrospinal fluid (CSF) biomarkers may aid the differentiation of these disorders, but other than α-synuclein and neurofilament light chain protein, which have limited diagnostic power, specific protein biomarkers remain elusive.Objectives To study disease mechanisms and identify possible CSF diagnostic biomarkers through discovery proteomics, which discriminate parkinsonian syndromes from healthy controls.Methods CSF was collected consecutively from 134 participants; Parkinson's disease (n = 26), atypical parkinsonian syndromes (n = 78, including progressive supranuclear palsy (n = 36), multiple system atrophy (n = 28), corticobasal syndrome (n = 14)), and elderly healthy controls (n = 30). Participants were divided into a discovery and a validation set for analysis. The samples were subjected to tryptic digestion, followed by liquid chromatography-mass spectrometry analysis for identification and relative quantification by isobaric labelling. Candidate protein biomarkers were identified based on the relative abundances of the identified tryptic peptides. Their predictive performance was evaluated by analysis of the validation set.Results 79 tryptic peptides, derived from 26 proteins were found to differ significantly between atypical parkinsonism patients and controls. They included acute phase/inflammatory markers and neuronal/synaptic markers, which were respectively increased or decreased in atypical parkinsonism, while their levels in PD subjects were intermediate between controls and atypical parkinsonism.Conclusion Using an unbiased proteomic approach, proteins were identified that were able to differentiate atypical parkinsonian syndrome patients from healthy controls. Our study indicates that markers that may reflect neuronal function and/or plasticity, such as the amyloid precursor protein, and inflammatory markers may hold future promise as candidate biomarkers in parkinsonism.
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NPTXR and NPTX1 were decreased in atypical parkinsonian disorders (progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration) in comparison with controls.
“Further to this, NPTXR and NPTX1 were decreased in atypical parkinsonian disorders (progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration) in comparison with controls (Magdalinou et al. 2017).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Magdalinou et al. 2017
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- Authors
- Magdalinou, N. K., Noyce, A. J., Pinto, R., Lindstrom, E., Holmén-Larsson, J., Holtta, M., Blennow, K., Morris, H. R., Skillbäck, T., Warner, T. T., Lees, A. J., Pike, I., Ward, M., Zetterberg, H., & Gobom, J.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- Umeå University (SE)
- University of Gothenburg (SE)
- The Royal Free Hospital (GB)
- Proteome Sciences (United Kingdom) (GB)
- Corresponding author
- Magdalinou, N.K.
- ORCID
- Venue
- Parkinsonism & Related Disorders
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 37
- Pages
- 65-71
- ISSN
- 1353-8020 (ISSN-L)
- OpenAlex
- W2583303566
- Cited by
- 49
- References
- 33
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 2
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- green
- qmro.qmul.ac.uk
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Parkinsonism & Related Disorders (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc-nd)
- Funders
- Swedish Research Council (521-2011-4709)
- Gun och Bertil Stohnes Stiftelse
- the Leonard Wolfson Experimental Neurology Centre
- Demensförbundet
- Stiftelsen för Gamla Tjänarinnor
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- cerebrospinal fluid biomarkers, parkinsonism
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Cohort Studies, Biomarkers, Neurofilament Proteins, Parkinsonian Disorders, Proteomics, alpha-Synuclein
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