van Dijk, KD, Bidinosti, M, Weiss, A, Raijmakers, P, Berendse, HW and van de Berg, WDJ (2014) Reduced alpha-synuclein levels in cerebrospinal fluid in Parkinson's disease are unrelated to clinical and imaging measures of disease severity. EUROPEAN JOURNAL OF NEUROLOGY. pp. 388-394.

Abstract

Background and purposeThe cerebrospinal fluid (CSF) concentration of -synuclein may reflect the aggregation of -synuclein in brain tissue that neuropathologically characterizes Parkinson's disease (PD). Although most studies in large cohorts report reduced CSF -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 -synuclein concentrations correlate with measures of disease severity. Acknowledging the methodological issues that emerged from previous studies, we evaluated whether CSF -synuclein levels differ between patients with PD and controls, and relate to disease duration or severity.Methods-Synuclein levels were measured in CSF samples of 53 well-characterized patients with PD and 50 healthy controls employing a recently developed time-resolved Forster's resonance energy transfer assay. In addition, we studied the relationship of CSF -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.ResultsIn patients with PD, we observed a decrease in mean CSF -synuclein levels that was unrelated to disease duration or measures of disease severity. Using total protein normalized -synuclein, a sensitivity and specificity of 70% and 74% could be reached for distinguishing between patients with PD and controls.ConclusionCSF -synuclein levels are reduced in patients with PD compared with healthy controls. However, sensitivity and specificity indicate that -synuclein will not suffice as a single biomarker. CSF -synuclein levels do not correlate with measures of disease severity, including striatal dopaminergic deficit.Click to view the accompanying paper in this issue

Item Type:	Article
Additional Information:	NIBR author: Bidinosti, M institute: NIBR contributor address: VU Univ Med Ctr Amsterdam, Dept Anat & Neurosci, Funct Neuroanat Sect, NL-1007 MB Amsterdam, Netherlands, Vrije Univ Amsterdam Med Ctr, Dept Neurol Neurosci, Amsterdam, Netherlands karin.vandijk@vumc.nl; Novartis Pharma AG, Novartis Inst Biomed Res, Basel, Switzerland ; Novartis Pharma AG, Novartis Inst Biomed Res, Basel, Switzerland, IRBM Promidis, Pomezia, Italy ; Vrije Univ Amsterdam Med Ctr, Dept Nucl Med & PET Res, Amsterdam, Netherlands ; Vrije Univ Amsterdam Med Ctr, Dept Neurol Neurosci, Amsterdam, Netherlands ; VU Univ Med Ctr Amsterdam, Dept Anat & Neurosci, Funct Neuroanat Sect, NL-1007 MB Amsterdam, Netherlands ; VU Univ Med Ctr Amsterdam, Dept Anat & Neurosci, Funct Neuroanat Sect, NL-1007 MB Amsterdam, Netherlands; Vrije Univ Amsterdam Med Ctr, Dept Neurol Neurosci, Amsterdam, Netherlands; van Dijk, KD; VU Univ Med Ctr Amsterdam, Dept Anat & Neurosci, Funct Neuroanat Sect, Neurosci Campus Amsterdam,POB 7057, NL-1007 MB Amsterdam, Netherlands
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22598