CSL Behring AG, Bern, Switzerland.
PLoS One. 2013 May 16;8(5):e63162. doi: 10.1371/journal.pone.0063162. Print 2013.
Intravenous Immunoglobulin (IVIG) has been proposed as a potential therapeutic for Alzheimer's disease (AD) and its efficacy is currently being tested in mild-to-moderate AD. Earlier studies reported the presence of anti-amyloid beta (Aβ) antibodies in IVIG. These observations led to clinical studies investigating the potential role of IVIG as a therapeutic agent in AD. Also, IVIG is known to mediate beneficial effects in chronic inflammatory and autoimmune conditions by interfering with various pathological processes. Therefore, we investigated the effects of IVIG and purified polyclonal Aβ-specific antibodies (pAbs-Aβ) on aggregation, toxicity and phagocytosis of Aβ in vitro, thus elucidating some of the potential mechanisms of action of IVIG in AD patients. We report that both IVIG and pAbs-Aβ specifically bound to Aβ and inhibited its aggregation in a dose-dependent manner as measured by Thioflavin T assay. Additionally, IVIG and the purified pAbs-Aβ inhibited Aβ-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line and prevented Aβ binding to rat primary cortical neurons. Interestingly, IVIG and pAbs-Aβ also increased the number of phagocytosing cells as well as the amount of phagocytosed fibrillar Aβ by BV-2 microglia. Phagocytosis of Aβ depended on receptor-mediated endocytosis and was accompanied by upregulation of CD11b expression. Importantly, we could also show that Privigen dose-dependently reversed Aβ-mediated LTP inhibition in mouse hippocampal slices. Therefore, our in vitro results suggest that IVIG may have an impact on different processes involved in AD pathogenesis, thereby promoting further understanding of the effects of IVIG observed in clinical studies.
静脉注射免疫球蛋白 (IVIG) 已被提议作为阿尔茨海默病 (AD) 的潜在治疗方法，其疗效目前正在轻度至中度 AD 中进行测试。早期研究报告了 IVIG 中存在抗淀粉样蛋白 β (Aβ) 抗体。这些观察结果导致了临床研究，调查 IVIG 作为 AD 治疗剂的潜在作用。此外，IVIG 通过干扰各种病理过程，已知在慢性炎症和自身免疫性疾病中具有有益作用。因此，我们研究了 IVIG 和纯化的多克隆 Aβ 特异性抗体 (pAbs-Aβ) 对体外 Aβ聚集、毒性和吞噬作用的影响，从而阐明了 IVIG 在 AD 患者中的一些潜在作用机制。我们报告说，IVIG 和 pAbs-Aβ 均特异性结合 Aβ，并以剂量依赖性方式抑制其聚集，如 Thioflavin T 测定所示。此外，IVIG 和纯化的 pAbs-Aβ 抑制了 SH-SY5Y 人神经母细胞瘤细胞系中 Aβ 诱导的神经毒性，并防止 Aβ 与大鼠原代皮质神经元结合。有趣的是，IVIG 和 pAbs-Aβ 还增加了吞噬细胞的数量以及 BV-2 小胶质细胞吞噬的纤维状 Aβ 的量。Aβ 的吞噬作用依赖于受体介导的内吞作用，并伴有 CD11b 表达的上调。重要的是，我们还可以表明，Privigen 以剂量依赖性方式逆转了小鼠海马切片中 Aβ 介导的 LTP 抑制。因此，我们的体外结果表明，IVIG 可能对 AD 发病机制中涉及的不同过程产生影响，从而促进进一步了解临床研究中观察到的 IVIG 的作用。
