title: CSF α-synuclein and UCH-L1 levels in Parkinson's disease and atypical parkinsonian disorders.
abstract: BACKGROUND
  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.
authors: Department of Neurosciences, University of Messina, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: stm_mondello@hotmail.com.
authors: Stefania
authors: S
authors: Mondello
authors: Department of Neurology, Sahlgrenska University Hospital, 41345 Göteborg, Sweden. Electronic address: Radu.Constantinescu@vgregion.se.
authors: Radu
authors: R
authors: Constantinescu
authors: Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, 43180 Mölndal, Sweden; UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
authors: Henrik
authors: H
authors: Zetterberg
authors: Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, 43180 Mölndal, Sweden.
authors: Ulf
authors: U
authors: Andreasson
authors: Department of Neurosciences, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
authors: Björn
authors: B
authors: Holmberg
authors: Atlantic Biomarkers, LLC, Gainesville, FL 32607, USA.
authors: Andreas
authors: A
authors: Jeromin
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid; D010300:Parkinson Disease / Q000134:cerebrospinal fluid; D020734:Parkinsonian Disorders / Q000134:cerebrospinal fluid*; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid; D024801:Tauopathies / Q000134:cerebrospinal fluid; D043222:Ubiquitin Thiolesterase / Q000134:cerebrospinal fluid*; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
chemical_list: D015415:Biomarkers; C482860:UCHL1 protein, human; D051844:alpha-Synuclein; D043222:Ubiquitin Thiolesterase
keywords: Atypical parkinsonian disorders; Cerebrospinal fluid; Parkinson's disease; UCH-L1; α-Synuclein