Stefania Mondello1, Radu Constantinescu2, Henrik Zetterberg3, Ulf Andreasson4, Björn Holmberg5, Andreas Jeromin6. 1. Department of Neurosciences, University of Messina, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: stm_mondello@hotmail.com. 2. Department of Neurology, Sahlgrenska University Hospital, 41345 Göteborg, Sweden. Electronic address: Radu.Constantinescu@vgregion.se. 3. Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, 43180 Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom. 4. Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, 43180 Mölndal, Sweden. 5. Department of Neurosciences, University of Messina, Via Consolare Valeria, 98125 Messina, Italy. 6. Atlantic Biomarkers, LLC, Gainesville, FL 32607, USA.
Abstract
INTRODUCTION: There is an unmet need for biomarkers for Parkinson's disease (PD) and atypical parkinsonian disorders (APD). α-Synuclein, linked to the pathogenesis of PD, is a promising biomarker candidate in need of further investigation. The ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a pivotal component of the ubiquitin proteasome system which seems to be disturbed in PD, may also be involved in the pathogenesis of this disorder. METHODS: We investigated cerebrospinal fluid (CSF) α-synuclein and UCH-L1 levels from 22 healthy controls, 52 patients with PD, 34 with multiple system atrophy (MSA), 32 with progressive supranuclear palsy, and 12 with corticobasal degeneration. RESULTS: α-Synuclein levels were significantly decreased in PD and in MSA compared with controls, and in synucleinopathies compared with tauopathies. UCH-L1 levels were significantly decreased in PD, MSA as well as PSP compared with controls, and in PD compared with APD (p < 0.001). Both markers discriminated PD well from controls (p < 0.0001; area under the curve [AUC] = 0.82 and 0.89, respectively). Additionally, CSF α-synuclein separated patients with synucleinopathies from those with tauopathies (p = 0.015; AUC = 0.63), whereas CSF UCH-L1 discriminated between PD and APD (p = 0.0003; AUC = 0.69). Interestingly, α-synuclein and UCH-L1 levels were strongly correlated in PD and synucleinopathies, and weakly in tauopathies. No correlation was found in controls. CONCLUSIONS: CSF levels of α-synuclein and UCH-L1 show distinct patterns in parkinsonian syndromes. Their combined determination may be useful in the differential diagnosis of parkinsonian disorders and provide key to understanding their pathoetiology and clinical course. Further large studies are needed to validate our findings.
INTRODUCTION: There is an unmet need for biomarkers for Parkinson's disease (PD) and atypical parkinsonian disorders (APD). α-Synuclein, linked to the pathogenesis of PD, is a promising biomarker candidate in need of further investigation. The ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a pivotal component of the ubiquitin proteasome system which seems to be disturbed in PD, may also be involved in the pathogenesis of this disorder. METHODS: We investigated cerebrospinal fluid (CSF) α-synuclein and UCH-L1 levels from 22 healthy controls, 52 patients with PD, 34 with multiple system atrophy (MSA), 32 with progressive supranuclear palsy, and 12 with corticobasal degeneration. RESULTS: α-Synuclein levels were significantly decreased in PD and in MSA compared with controls, and in synucleinopathies compared with tauopathies. UCH-L1 levels were significantly decreased in PD, MSA as well as PSP compared with controls, and in PD compared with APD (p < 0.001). Both markers discriminated PD well from controls (p < 0.0001; area under the curve [AUC] = 0.82 and 0.89, respectively). Additionally, CSF α-synuclein separated patients with synucleinopathies from those with tauopathies (p = 0.015; AUC = 0.63), whereas CSF UCH-L1 discriminated between PD and APD (p = 0.0003; AUC = 0.69). Interestingly, α-synuclein and UCH-L1 levels were strongly correlated in PD and synucleinopathies, and weakly in tauopathies. No correlation was found in controls. CONCLUSIONS: CSF levels of α-synuclein and UCH-L1 show distinct patterns in parkinsonian syndromes. Their combined determination may be useful in the differential diagnosis of parkinsonian disorders and provide key to understanding their pathoetiology and clinical course. Further large studies are needed to validate our findings.
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