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Reduced α‐synuclein levels in cerebrospinal fluid in P arkinson's disease are unrelated to clinical and imaging measures of disease severity
Author(s) -
Dijk K. D.,
Bidinosti M.,
Weiss A.,
Raijmakers P.,
Berendse H. W.,
Berg W. D. J.
Publication year - 2014
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12176
Subject(s) - cerebrospinal fluid , medicine , biomarker , disease , confounding , parkinson's disease , dopamine transporter , dopaminergic , gastroenterology , pathology , case control study , oncology , dopamine , biology , biochemistry
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.