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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.
Glossary
- α-Syn=
- α-synuclein;
- α-Syn-nAbs=
- naturally occurring autoantibodies against α-synuclein;
- AD=
- Alzheimer disease;
- BSA=
- bovine serum albumin;
- CI=
- confidence interval;
- CV=
- coefficient of variation;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- H&Y=
- Hoehn & Yahr;
- HC=
- healthy controls;
- IVIg=
- IV immunoglobulin G;
- PBS=
- phosphate-buffered saline;
- PD=
- Parkinson disease;
- RBC=
- red blood cells;
- ROC=
- receiver operating characteristic;
- RT=
- room temperature
Footnotes
↵* These authors contributed equally to this work.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received March 31, 2012.
- Accepted August 21, 2012.
- © 2013 American Academy of Neurology
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