Reduced α‐synuclein levels in cerebrospinal fluid in P arkinson's disease are unrelated to clinical and imaging measures of disease severity

• Published in: European journal of neurology Vol. 21; no. 3; pp. 388 - 394
• Main Authors: van Dijk, K. D., Bidinosti, M., Weiss, A., Raijmakers, P., Berendse, H. W., van de Berg, W. D. J.
• Format: Journal Article
• Language: English
• Published: 01-03-2014
• ISSN: 1351-5101; 1468-1331
• DOI: 10.1111/ene.12176

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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