Laboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry, University of Konstanz, Konstanz, Germany.
PLoS One. 2013 Jul 18;8(7):e68996. doi: 10.1371/journal.pone.0068996. Print 2013.
Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.
最近的研究表明，生理性β-淀粉样蛋白自身抗体（Aβ-自身抗体）在阿尔茨海默病（AD）中具有保护作用。然而，迄今为止，在血清中测定游离和游离的 Aβ-自身抗体，其功能和可能的生物标志物价值的结果并不一致。在这里，我们报告了一种新的夹心酶联免疫吸附测定（ELISA）在 112 名 AD 患者和年龄及性别匹配的对照组的血清和脑脊液（CSF）中测定结合抗原的 Aβ-自身抗体（完整的 Aβ-IgG 免疫复合物）的应用。与对照组相比，AD 患者的血清和 CSF 中 Aβ-IgG 免疫复合物水平均显著升高。此外，Aβ-IgG 复合物的水平与各组的认知状态呈负相关，随着受试者认知测试表现的下降而增加。我们的研究结果表明 IgG 型自身抗体对体内 Aβ 清除的贡献，以及 AD 中免疫反应的增加，这可能与 Aβ-IgG 清除不足有关。这些发现可能有助于阐明 Aβ-自身抗体在 AD 病理生理学中的作用及其在 AD 诊断中的潜在应用。
