Current therapies to treat Alzheimer's disease (AD) are focused on ameliorating symptoms instead of treating the underlying causes of AD. The accumulation of amyloid β (Aβ) oligomers, whether by an increase in production or by a decrease in clearance, has been described as the seed that initiates the pathological cascade in AD. Developing therapies to target these species is a vital step in improving AD treatment. Aβ-immunotherapy, especially passive immunotherapy, is a promising approach to reduce the Aβ burden. Up to now, several monoclonal antibodies (mAbs) have been tested in clinical trials on humans, but none of them have passed Phase III. In all likelihood, these trials failed mainly because patients with mild-to-moderate AD were recruited, and thus treatment may have been too late to be effective. Therefore, many ongoing clinical trials are being conducted in patients at the prodromal stage. New structures based on antibody fragments have been engineered intending to improve efficacy and safety. This review presents the properties of this variety of developing treatments and provides a perspective on state-of-the-art of passive Aβ-immunotherapy in AD.

中文翻译：

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Aβ-免疫治疗策略：广泛的阿尔茨海默病治疗方法

目前治疗阿尔茨海默病 (AD) 的疗法集中在改善症状而不是治疗 AD 的根本原因。淀粉样蛋白的积累β（一种β) 寡聚体，无论是通过增加产量还是通过减少清除率，都被描述为启动 AD 病理级联反应的种子。开发针对这些物种的疗法是改善 AD 治疗的重要一步。一种β-免疫疗法，尤其是被动免疫疗法，是降低 Aβ负担。截至目前，已有多种单克隆抗体（mAbs）在人体临床试验中进行了测试，但均未通过III期临床试验。这些试验极有可能失败，主要是因为招募了轻度至中度 AD 患者，因此治疗可能为时已晚而无法奏效。因此，许多正在进行的临床试验正在前驱期的患者中进行。已经设计了基于抗体片段的新结构，旨在提高功效和安全性。这篇综述介绍了这种发展中的治疗方法的特性，并提供了关于被动 A 的最新技术的观点β-AD中的免疫疗法。