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

Authors

  • K. D. van Dijk,

    Corresponding author
    1. Department of Anatomy and Neurosciences, Section of Functional Neuroanatomy, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
    2. Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
    • Correspondence: K. D. van Dijk, Department of Anatomy and Neurosciences, Section Functional Neuroanatomy, Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, PO Box 7057, 1007 MB Amsterdam, The Netherlands (tel.: +31204446179; fax: +31204448054; e-mail: karin.vandijk@vumc.nl).

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  • M. Bidinosti,

    1. Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
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  • A. Weiss,

    1. Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
    2. IRBM Promidis, Pomezia, Italy
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  • P. Raijmakers,

    1. Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands
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  • H. W. Berendse,

    1. Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
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  • W. D. J. van de Berg

    1. Department of Anatomy and Neurosciences, Section of Functional Neuroanatomy, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
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  • See editorial by Zetterberg et al. on page 365.

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.

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