title: Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease.
abstract: OBJECTIVE
  Biomarkers are required for the diagnosis and monitoring of disease progression in Parkinson disease (PD). To date, most studies have concentrated on α-synuclein (α-Syn), a protein involved in Parkinson disease pathogenesis, as a potential biomarker, with inconsistent outcomes. Recently, naturally occurring autoantibodies against α-Syn (α-Syn-nAbs) have been detected in the serum of patients with PD. They represent a putative diagnostic marker for PD.
  
  
  METHODS
  We established and validated an ELISA to quantify α-Syn-nAbs in serum samples. We analyzed serum samples from 62 patients with PD, 46 healthy controls (HC), and 42 patients with Alzheimer disease (AD) using this newly established ELISA. Additionally, serum levels of endogenous α-Syn were measured.
  
  
  RESULTS
  There was a significant difference in α-Syn-nAbs levels between the investigated groups (p = 0.005; Kruskal-Wallis test). Levels of α-Syn-nAbs were significantly lower in patients with PD compared to HC (p < 0.05; Dunn multiple comparison post hoc test) or patients with AD (p < 0.05). Furthermore, we detected no difference between patients with AD and HC. The sensitivity and specificity of the assay for patients with PD vs. HC were 85% and 25%, respectively. The α-Syn-nAbs levels did not correlate with age, Hoehn & Yahr status, or duration of disease. Endogenous α-Syn had no influence on α-Syn-nAbs levels in sera.
  
  
  CONCLUSIONS
  Using a well-validated assay, we detected reduced α-Syn-nAbs levels in patients with PD compared to patients with AD and HC. The assay did not achieve criteria for use as a diagnostic tool to reliably distinguish PD from HC. Further studies are needed to assess α-Syn-nAbs as a biomarker in PD.
authors.affiliation: Department of Neurology, Philipps-University Marburg, Marburg.
authors.forename: Daniela
authors.initials: D
authors.lastname: Besong-Agbo
authors.forename: Elias
authors.initials: E
authors.lastname: Wolf
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Matthias
authors.initials: M
authors.lastname: Oechsner
authors.forename: Eva
authors.initials: E
authors.lastname: Hametner
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Carmen
authors.initials: C
authors.lastname: Noelker
authors.forename: Michael
authors.initials: M
authors.lastname: Bacher
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000097:blood / Q000276:immunology*; D012372:ROC Curve; D015203:Reproducibility of Results; D051844:alpha-Synuclein / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D051844:alpha-Synuclein