Solomon Beka
Department of Molecular Microbiology and Biotechnology, George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Tel Aviv, Israel.
Curr Opin Mol Ther. 2007 Feb;9(1):79-85.
Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.
β淀粉样肽（Aβ）促成阿尔茨海默病（AD）的急性进展，已成为治疗的主要靶点。在AD患者中用Aβ进行主动免疫已显示出疗效；然而，一些患者出现了副作用，可能与自身免疫反应有关。本文综述了静脉注射免疫球蛋白（IVIg）的相关证据，IVIg是一种经美国食品药品监督管理局批准的从正常人献血者血液中纯化的免疫球蛋白组分，显示出对AD进行被动免疫治疗的前景。利用BV-2细胞系小胶质细胞对IVIg对Aβ清除的分子效应进行的研究表明，IVIg在体外可溶解Aβ纤维，增加细胞对Aβ的耐受性，增强小胶质细胞向Aβ沉积物的迁移，并介导Aβ的吞噬作用。初步临床结果表明，含有针对Aβ的天然抗体的IVIg值得进一步研究其对该肽进行可控免疫攻击的潜力，避免对Aβ疫苗首次临床试验产生负面影响的免疫毒性。
