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Eur J Neurol. 2014 Mar;21(3):388-94. doi: 10.1111/ene.12176. Epub 2013 Apr 30.

Reduced α-synuclein levels in cerebrospinal fluid in Parkinson's disease are unrelated to clinical and imaging measures of disease severity.

Author information

1
Department of Anatomy and Neurosciences, Section of Functional Neuroanatomy, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands; Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.

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 Förster'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.

KEYWORDS:

DAT-SPECT; Parkinson's disease; biomarker; cerebrospinal fluid; α-synuclein

PMID:
23631635
DOI:
10.1111/ene.12176
[Indexed for MEDLINE]

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