Center of Neurology, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
J Alzheimers Dis. 2011;26(1):171-9. doi: 10.3233/JAD-2011-110221.
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.
越来越多的证据表明，在路易体相关痴呆症（包括帕金森病伴痴呆（PDD）和路易体痴呆症（DLB））中，适应性免疫系统发生改变，退行性过程除了神经元结构外还包括神经胶质细胞。因此，我们旨在确定这些痴呆症类型中针对淀粉样蛋白和神经胶质衍生结构的自身抗体水平。我们使用新开发的酶联免疫吸附测定（ELISA），测量了血清和脑脊液中总共 91 名受试者（13 名 PDD、14 名 DLB、11 名阿尔茨海默病（AD）、11 名额颞叶痴呆（FTD）、11 名血管性痴呆患者（VaD）和 31 名健康对照者）针对神经元和神经胶质结构的 IgG 自身抗体水平。测定了针对α-突触核蛋白、淀粉样蛋白-β₄₂（Aβ₄₂）、髓鞘少突胶质细胞糖蛋白（MOG）、髓鞘碱性蛋白（MBP）和 S100B 的自身抗体水平。在所有组中，血清中的自身抗体水平比脑脊液中的水平高约三个数量级。与tau 相关的痴呆症（AD、FTD）、VaD 和对照组相比，PDD/DLB 患者血清中针对α-突触核蛋白、Aβ₄₂、MOG、MBP 和 S100B 的自身抗体水平更高，其中大多数达到了非常显著的 p 值。在脑脊液（CSF）中，PDD/DLB 患者中针对少突胶质细胞衍生抗原（MOG、MBP）的抗体水平显著升高。在路易体相关痴呆症患者的血清和脑脊液中，针对神经元和神经胶质衍生抗原的自身抗体水平升高，表明这些痴呆症类型中适应性免疫系统的活性发生改变。神经源性 IgG 自身抗体作为路易体相关痴呆症诊断生物标志物组合的一部分的潜力应进一步评估。
