title: Naturally occurring alpha-synuclein autoantibodies in Parkinson's disease: sources of (error) variance in biomarker assays.
abstract: Alpha-synuclein (α-Syn) plays a pivotal role in the pathophysiology of Parkinson's disease (PD), which can partly be modulated by innate and adaptive immune functions, and vice versa. Here, naturally occurring α-Syn autoantibodies (α-Syn-nAbs) may be effective against α-Syn pathoetiology and may serve as a PD biomarker. However, serum and cerebrospinal fluid α-Syn-nAbs levels still lack consistent evidence as required for a reliable PD biomarker. Serum and cerebrospinal fluid α-Syn-nAbs levels of 66 PD patients and 69 healthy controls were assessed using a validated ELISA assay. Moreover, potential sources of error variance including unspecific ELISA background signals, free serum hemoglobin concentrations, α-Syn plate coating procedures, and differences in α-Syn-nAbs standards, were investigated. PD patients and controls did not differ in serum (p = .49) nor cerebrospinal fluid (p = .29) α-Syn-nAbs levels. Interestingly, free serum hemoglobin concentrations were negatively correlated with α-Syn-nAbs levels in controls (Spearman ρ = -.41, p<.001), but not in PD patients (ρ = .16, p = .21). ELISA α-Syn plate coating procedures impacted inter-assay variability (same day coating: 8-16%; coating on different days: 16-58%). α-Syn-nAbs standards from different purification batches differed regarding optical density measured in ELISAs suggesting differences in α-Syn affinity. While α-Syn-nAbs levels may represent a potential PD biomarker, several methodological issues have to be considered to increase reproducibility of α-Syn-nAbs findings. Further studies using standardized protocols minimizing sources of error variance may be necessary to establish a reliable PD α-Syn-nAbs biomarker.
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heinzel
authors.affiliation: Department of Neurology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Gold
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Deuschle
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bernhard
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.affiliation: Department of Neurodegeneration, Hertie Institute for Clinical Brain Research (HIH), University of Tuebingen, Tuebingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tuebingen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.affiliation: Department of Neurology, Philipps-University Marburg, Marburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Dodel
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology*; D051844:alpha-Synuclein / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D051844:alpha-Synuclein