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Published in: Translational Neurodegeneration 1/2019

Open Access 01-12-2019 | Dementia | Research

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

Authors: Franziska Hopfner, Stefanie H. Müller, 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, Jörg B. Schulz, Annika Spottke, Alexander Storch, Claudia Trenkwalder, Hans-Ulrich Wittchen, Karsten Witt, Ullrich Wüllner, Günther Deuschl, Gregor Kuhlenbäumer

Published in: Translational Neurodegeneration | Issue 1/2019

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Abstract

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.
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Literature
2.
go back to reference Dzamko N, Geczy CL, Halliday GM. Inflammation is genetically implicated in Parkinson's disease. Neuroscience. 2015;302:89–102.CrossRefPubMed Dzamko N, Geczy CL, Halliday GM. Inflammation is genetically implicated in Parkinson's disease. Neuroscience. 2015;302:89–102.CrossRefPubMed
3.
4.
go back to reference Dahm L, Ott C, Steiner J, et al. Seroprevalence of autoantibodies against brain antigens in health and disease. Ann Neurol. 2014;76(1):82–94.CrossRefPubMed Dahm L, Ott C, Steiner J, et al. Seroprevalence of autoantibodies against brain antigens in health and disease. Ann Neurol. 2014;76(1):82–94.CrossRefPubMed
5.
go back to reference Doss S, Wandinger KP, Hyman BT, et al. High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types. Ann Clin Transl Neurol. 2014;1(10):822–32.CrossRefPubMedPubMedCentral Doss S, Wandinger KP, Hyman BT, et al. High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types. Ann Clin Transl Neurol. 2014;1(10):822–32.CrossRefPubMedPubMedCentral
6.
go back to reference Krawczak M, Nikolaus S, von Eberstein H, Croucher PJ, El Mokhtari NE, Schreiber S. PopGen: population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships. Community Genet. 2006;9(1):55–61.PubMed Krawczak M, Nikolaus S, von Eberstein H, Croucher PJ, El Mokhtari NE, Schreiber S. PopGen: population-based recruitment of patients and controls for the analysis of complex genotype-phenotype relationships. Community Genet. 2006;9(1):55–61.PubMed
7.
go back to reference Balzer-Geldsetzer M, Costa AS, Kronenburger M, et al. Parkinson’s disease and dementia: a longitudinal study (DEMPARK). Neuroepidemiology. 2011;37(3–4):168–76.CrossRefPubMed Balzer-Geldsetzer M, Costa AS, Kronenburger M, et al. Parkinson’s disease and dementia: a longitudinal study (DEMPARK). Neuroepidemiology. 2011;37(3–4):168–76.CrossRefPubMed
8.
go back to reference Kasten M, Bruggemann N, Schmidt A, Klein C. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology. 2010;75(5):478 author reply 478-479.CrossRefPubMed Kasten M, Bruggemann N, Schmidt A, Klein C. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology. 2010;75(5):478 author reply 478-479.CrossRefPubMed
9.
go back to reference Kalbe E, Calabrese P, Kohn N, et al. Screening for cognitive deficits in Parkinson’s disease with the Parkinson neuropsychometric dementia assessment (PANDA) instrument. Parkinsonism Relat Disord. 2008;14(2):93–101.CrossRefPubMed Kalbe E, Calabrese P, Kohn N, et al. Screening for cognitive deficits in Parkinson’s disease with the Parkinson neuropsychometric dementia assessment (PANDA) instrument. Parkinsonism Relat Disord. 2008;14(2):93–101.CrossRefPubMed
10.
go back to reference Karrasch M, Laatu S, Martikainen K, Marttila R. CERAD test performance and cognitive impairment in Parkinson’s disease. Acta Neurol Scand. 2013;128(6):409–13.CrossRefPubMed Karrasch M, Laatu S, Martikainen K, Marttila R. CERAD test performance and cognitive impairment in Parkinson’s disease. Acta Neurol Scand. 2013;128(6):409–13.CrossRefPubMed
12.
go back to reference Kalbe E, Rehberg SP, Heber I, et al. Subtypes of mild cognitive impairment in patients with Parkinson’s disease: evidence from the LANDSCAPE study. J Neurol Neurosurg Psychiatry. 2016;87(10):1099–105.CrossRefPubMed Kalbe E, Rehberg SP, Heber I, et al. Subtypes of mild cognitive impairment in patients with Parkinson’s disease: evidence from the LANDSCAPE study. J Neurol Neurosurg Psychiatry. 2016;87(10):1099–105.CrossRefPubMed
13.
go back to reference Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord. 2007;22(12):1689–707 quiz 1837.CrossRefPubMed Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord. 2007;22(12):1689–707 quiz 1837.CrossRefPubMed
14.
go back to reference Hammer C, Stepniak B, Schneider A, et al. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity. Mol Psychiatry. 2014;19(10):1143–9.CrossRefPubMed Hammer C, Stepniak B, Schneider A, et al. Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity. Mol Psychiatry. 2014;19(10):1143–9.CrossRefPubMed
Metadata
Title
No association between Parkinson disease and autoantibodies against NMDA-type glutamate receptors
Authors
Franziska Hopfner
Stefanie H. Müller
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
Jörg B. Schulz
Annika Spottke
Alexander Storch
Claudia Trenkwalder
Hans-Ulrich Wittchen
Karsten Witt
Ullrich Wüllner
Günther Deuschl
Gregor Kuhlenbäumer
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Translational Neurodegeneration / Issue 1/2019
Electronic ISSN: 2047-9158
DOI
https://doi.org/10.1186/s40035-019-0153-0

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