Reduced α‐synuclein levels in cerebrospinal fluid in P arkinson's disease are unrelated to clinical and imaging measures of disease severity
Abstract
Background and purpose: The cerebrospinal fluid (CSF) concentration of α‐synuclein may reflect the aggregation of α‐synuclein in brain tissue that neuropathologically characterizes Parkinson's disease (PD). Although most studies in large cohorts report reduced CSF α‐synuclein levels in PD, the available data to date are not consistent due to variation in group sizes, pre‐analytical confounding factors and assay characteristics. Furthermore, it remains unclear whether CSF α‐synuclein concentrations correlate with measures of disease severity. Acknowledging the methodological issues that emerged from previous studies, we evaluated whether CSF α‐synuclein levels differ between patients with PD and controls, and relate to disease duration or severity. Methods: α‐Synuclein levels were measured in CSF samples of 53 well‐characterized patients with PD and 50 healthy controls employing a recently developed time‐resolved F örster's resonance energy transfer assay. In addition, we studied the relationship of CSF α‐synuclein levels with disease duration, clinical measures of disease severity and the striatal dopaminergic deficit as measured by dopamine transporter binding and single photon emission computed tomography. Results: In patients with PD, we observed a decrease in mean CSF α‐synuclein levels that was unrelated to disease duration or measures of disease severity. Using total protein normalized α‐synuclein, a sensitivity and specificity of 70% and 74% could be reached for distinguishing between patients with PD and controls. Conclusion: CSF α‐synuclein levels are reduced in patients with PD compared with healthy controls. However, sensitivity and specificity indicate that α‐synuclein will not suffice as a single biomarker. CSF α‐synuclein levels do not correlate with measures of disease severity, including striatal dopaminergic deficit.
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Reduced cerebrospinal fluid αSyn levels do not appear to be associated with clinical or imaging measures of Parkinson's disease severity.
“reduced CSF αSyn levels do not appear to be associated with clinical or imaging measures of PD severity [95].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [95]
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- Authors
- van Dijk, K. D., Bidinosti, M., Weiss, A., Raijmakers, P., Berendse, H. W., & van de Berg, W. D. J.
- Affiliations
- Department of Anatomy and Neurosciences Section of Functional Neuroanatomy Neuroscience Campus Amsterdam VU University Medical Center Amsterdam The Netherlands
- Novartis (Switzerland) (CH)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Amsterdam Neuroscience (NL)
- Venue
- European Journal of Neurology
- Publisher
- Wiley
- Published
- 2013-04-30
- Volume
- 21
- Issue
- 3
- Pages
- 388-394
- ISSN
- 1351-5101 (ISSN-L)
- 1468-1331
- OpenAlex
- W2000234908
- Cited by
- 88
- References
- 26
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 9 · 2015: 12 · 2014: 11 · 2013: 3
- FWCI
- 7.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Parkinson's disease, alpha-synuclein, cerebrospinal fluid biomarkers, disease severity, disease duration, dopamine transporter imaging, sensitivity and specificity
- MeSH terms
- Adult, Aged, Aged, 80 and over, Corpus Striatum, Female, Humans, Male, Mental Status Schedule, Middle Aged, Parkinson Disease, Retrospective Studies, ROC Curve, Tomography, Emission-Computed, Single-Photon, Case-Control Studies, Statistics, Nonparametric, Fluorescence Resonance Energy Transfer, Dopamine Plasma Membrane Transport Proteins, alpha-Synuclein
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