With the advent of the first disease-modifying, anti-amyloid β-directed passive immunotherapy for Alzheimer's disease, questions arise who, when, and how to treat. This paper describes shortly the pathogenic basis of and preclinical data, which have, more than two decades ago, initiated the development of this vaccination therapy. We discuss clinical trial results of aducanumab, lecanemab, and donanemab. We also review appropriate use recommendations of these novel treatments on patient selection and safety monitoring. Furthermore, estimations of numbers of patient who will qualify for treatment regarding inclusion and exclusion criteria and estimations on readiness of health-care systems for identifying the right patients and for providing the treatment are reported. In our view, we are experiencing a fundamental shift from syndrome-based Alzheimer's dementia care to early, biomarker-guided treatment of Alzheimer's disease. This shift requires substantial adjustments of infrastructure and resources, but also holds promise of eventually achieving substantial slowing of disease progression and delaying dementia.

中文翻译：

---

阿尔茨海默病的被动抗淀粉样蛋白β免疫疗法——机遇与挑战


随着阿尔茨海默病首个针对疾病改善疾病的抗淀粉样蛋白β定向被动免疫疗法的问世，出现了由谁治疗、何时治疗以及如何治疗的问题。本文简要描述了二十多年前启动这种疫苗接种疗法开发的致病基础和临床前数据。我们讨论了 aducanumab、lecanemab 和 donanemab 的临床试验结果。我们还回顾了这些新疗法在患者选择和安全监测方面的适当使用建议。此外，还报告了根据纳入和排除标准对符合治疗条件的患者人数的估计，以及对医疗保健系统确定合适患者和提供治疗的准备情况的估计。在我们看来，我们正在经历从基于综合征的阿尔茨海默病痴呆护理到早期生物标志物指导的阿尔茨海默病治疗的根本转变。这种转变需要对基础设施和资源进行大量调整，但也有望最终大幅减缓疾病进展和延缓痴呆症。