Autoantibodies Against Amyloid and Glial-Derived Antigens are Increased in Serum and Cerebrospinal Fluid of Lewy Body-Associated Dementias

Article type: Research Article

Authors: Maetzler, Walter^{a; b; c; 1; *} | Berg, Daniela^{a; b; 1} | Synofzik, Matthis^{a; b} | Brockmann, Kathrin^{a; b} | Godau, Jana^{a; b} | Melms, Arthur^d | Gasser, Thomas^{a; b} | Hörnig, Stephanie^e | Langkamp, Markus^f

Affiliations: [a] Center of Neurology, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany | [b] German Center for Neurodegenerative Diseases (DZNE), University of Tuebingen, Tuebingen, Germany | [c] Department of Geriatric Rehabilitation, Robert-Bosch-Hospital, Stuttgart, Germany | [d] Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany | [e] GMBU eV, Halle, Germany | [f] Mediagnost, Reutlingen, Germany

Correspondence: [*] Correspondence to: Walter Maetzler, MD, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe Seyler-Strasse 3, 72076 Tuebingen, Germany. Tel.: +49 7071 2982047; Fax: +49 7071 294617; E-mail: walter.maetzler@uni-tuebingen.de.

Note: [1] These authors contributed equally.

Abstract: There is increasing evidence that in Lewy body-associated dementias (encompassing Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB)), the adaptive immune system is altered and the degenerative process includes glial cells in addition to neuronal structures. We therefore aimed to determine levels of autoantibodies against amyloid and glial-derived structures in these dementia types. Using a newly developed Enzyme-linked immunosorbent assay (ELISA), we measured levels of IgG autoantibodies against neuronal and glial structures in serum and cerebrospinal fluid of a total of 91 subjects (13 PDD, 14 DLB, 11 Alzheimer's disease (AD), 11 frontotemporal dementia (FTD), 11 vascular dementia patients (VaD), and 31 healthy controls). Autoantibody levels against α-synuclein, amyloid-β42 (Aβ42), myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and S100B were determined. In all groups, autoantibody levels were about three magnitudes higher in serum than in CSF. Serum autoantibody levels against α-synuclein, Aβ42, MOG, MBP, and S100B were higher in PDD/DLB compared to tau-associated dementias (AD, FTD), VaD, and controls, respectively, with most of them reaching highly significant p-values. In cerebrospinal fluid (CSF), levels of antibodies against oligodendrocyte-derived antigens (MOG, MBP) were significantly increased in PDD/DLB. Increased levels of autoantibodies against both neuronal- and glial-derived antigens in serum and CSF of Lewy body-associated dementias indicate an altered activity of the adaptive immune system in these dementia types. The potential of neural-derived IgG autoantibodies as part of a biomarker panel for the diagnosis of Lewy body-associated dementias should be further evaluated.

Keywords: Astrocytes, autoantibodies, dementia with Lewy bodies, glial cells, Lewy body disease, oligodendrocytes, Parkinson's disease dementia

DOI: 10.3233/JAD-2011-110221

Journal: Journal of Alzheimer's Disease, vol. 26, no. 1, pp. 171-179, 2011