a Center for Cognitive Neurology , New York University School of Medicine , New York , NY , USA.
b Departments of Neurology , New York University School of Medicine , New York , NY , USA.
Expert Rev Vaccines. 2018 Aug;17(8):707-721. doi: 10.1080/14760584.2018.1500905. Epub 2018 Aug 9.
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by protein aggregates of amyloid β (Aβ) and tau. These proteins have normal physiological functions, but in AD, they undergo a conformational change and aggregate as toxic oligomeric and fibrillar species with a high β-sheet content.
Active and passive immunotherapeutic approaches are among the most attractive methods for targeting misfolded Aβ and tau. Promising preclinical testing of various immunotherapeutic approaches has yet to translate to cognitive benefits in human clinical trials. Knowledge gained from these past failures has led to the development of second-generation Aβ-active immunotherapies, anti-Aβ monoclonal antibodies targeting a wide array of Aβ conformations, and to a number of immunotherapies targeting pathological tau. This review covers the more recent advances in vaccine development for AD from 2016 to present.
Due to the complex pathophysiology of AD, greatest clinical efficacy will most likely be achieved by concurrently targeting the most toxic forms of both Aβ and tau.
阿尔茨海默病（AD）是一种破坏性的神经退行性疾病，其特征是淀粉样蛋白β（Aβ）和 tau 的蛋白聚集体。这些蛋白质具有正常的生理功能，但在 AD 中，它们发生构象变化，并聚集成具有高β-折叠含量的毒性寡聚体和纤维状物质。
主动和被动免疫治疗方法是针对错误折叠的 Aβ 和 tau 的最有吸引力的方法之一。各种免疫治疗方法的有希望的临床前测试尚未转化为人类临床试验中的认知益处。从这些过去的失败中获得的知识导致了第二代 Aβ 主动免疫疗法、针对广泛 Aβ 构象的抗 Aβ 单克隆抗体以及针对病理性 tau 的许多免疫疗法的发展。这篇综述涵盖了 2016 年至今 AD 疫苗开发的最新进展。
由于 AD 的复杂病理生理学，最有可能通过同时针对 Aβ 和 tau 中最有毒的形式来获得最大的临床疗效。
