No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors


Franziska Hopfner, Stefanie Muller, Dagmar Steppat, Joanna Miller, Nele Schmidt, Klaus-Peter Wandinger, Frank Leypoldt, Daniela Berg, Andre Franke, Wolfgang Lieb, Lukas Tittmann, Monika Balzer-Geldsetzer, Simon Baudrexel, Richard Dodel, Ruediger Hilker-Roggendorf, Elke Kalbe, Jan Kassubek, Thomas Klockgether, Inga Liepelt-Scarfone, Brit Mollenhauer, Petra Neuser, Kathrin Reetz, Oliver Riedel, Claudia Schulte, Jorg Schulz, Annika Spottke, Alexander Storch, Claudia Trenkwalder, Hans-Ulrich Wittchen, Karsten Witt, Ullrich Wullner, Gunther Deuschl, Gregor Kuhlenbaumer




Translational neurodegeneration




Background: IgG-class autoantibodies to N-Methyl-D-Aspartate (NMDA)-type glutamate receptors define a novel entity of autoimmune encephalitis. Studies examining the prevalence of NMDA IgA/IgM antibodies in patients with Parkinson disease with/without dementia produced conflicting results. We measured NMDA antibodies in a large, well phenotyped sample of Parkinson patients without and with cognitive impairment (n = 296) and controls (n = 295) free of neuropsychiatric disease. Detailed phenotyping and large numbers allowed statistically meaningful correlation of antibody status with diagnostic subgroups as well as quantitative indicators of disease severity and cognitive impairment. Methods: NMDA antibodies were analysed in the serum of patients and controls using well established validated assays. We used anti-NMDA antibody positivity as the main independent variable and correlated it with disease status and phenotypic characteristics. Results: The frequency of NMDA IgA/IgM antibodies was lower in Parkinson patients (13%) than in controls (22%) and higher than in previous studies in both groups. NMDA IgA/IgM antibodies were neither significantly associated with diagnostic subclasses of Parkinson disease according to cognitive impairment, nor with quantitative indicators of disease severity and cognitive impairment. A positive NMDA antibody status was positively correlated with age in controls but not in Parkinson patients. Conclusion: It is unlikely albeit not impossible that NMDA antibodies play a significant role in the pathogenesis or progression of Parkinson disease e.g. to Parkinson disease with dementia, while NMDA IgG antibodies define a separate disease of its own.