National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The Second Affiliated Hospital and Yuying Children's Hospital, Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Signal Transduct Target Ther. 2023 Jun 30;8(1):248. doi: 10.1038/s41392-023-01484-7.
Amyloid β protein (Aβ) is the main component of neuritic plaques in Alzheimer's disease (AD), and its accumulation has been considered as the molecular driver of Alzheimer's pathogenesis and progression. Aβ has been the prime target for the development of AD therapy. However, the repeated failures of Aβ-targeted clinical trials have cast considerable doubt on the amyloid cascade hypothesis and whether the development of Alzheimer's drug has followed the correct course. However, the recent successes of Aβ targeted trials have assuaged those doubts. In this review, we discussed the evolution of the amyloid cascade hypothesis over the last 30 years and summarized its application in Alzheimer's diagnosis and modification. In particular, we extensively discussed the pitfalls, promises and important unanswered questions regarding the current anti-Aβ therapy, as well as strategies for further study and development of more feasible Aβ-targeted approaches in the optimization of AD prevention and treatment.
淀粉样β蛋白（Aβ）是阿尔茨海默病（AD）中神经纤维缠结的主要成分，其积累被认为是阿尔茨海默病发病机制和进展的分子驱动因素。Aβ一直是 AD 治疗开发的主要靶点。然而，Aβ 靶向临床试验的反复失败，使人们对淀粉样蛋白级联假说以及阿尔茨海默病药物的开发是否遵循正确的方向产生了相当大的怀疑。然而，最近 Aβ 靶向试验的成功缓解了这些疑虑。在这篇综述中，我们讨论了过去 30 年来淀粉样蛋白级联假说的演变，并总结了其在阿尔茨海默病诊断和修饰中的应用。特别是，我们广泛讨论了当前抗 Aβ 治疗的缺陷、承诺和重要的未解决问题，以及进一步研究和开发更可行的 Aβ 靶向方法的策略，以优化 AD 的预防和治疗。
