Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.
Sci China Life Sci. 2021 Jun;64(6):926-937. doi: 10.1007/s11427-020-1810-y. Epub 2020 Oct 23.
Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer's disease (AD) and has been regarded as the main therapeutic target for AD. However, most of the Aβ-targeted clinical trials have not succeeded. Therefore, the Aβ-targeted therapeutic strategy on treating this complex disease needs to be re-evaluated. In this review, we analyzed the challenges and critical points of the current anti-Aβ therapeutic strategies. In addition to Aβ, multiple pathological events such as tau hyperphosphorylation, oxidative stress, and neuroinflammation, which are involved in AD pathogenesis and synergistically drive disease progression, could be important targets for AD treatment. Tertiary prevention strategies are needed for the successful management of AD due to its complex and dynamic pathogenesis. Systemic perspective addressing the disease pathogenesis within and outside the brain, as well as the multidomain intervention targeting risk factors and comorbidities, are important approaches for the therapeutic solutions of AD.
淀粉样蛋白-β（Aβ）在阿尔茨海默病（AD）的发病机制中起着关键作用，已被视为 AD 的主要治疗靶点。然而，大多数针对 Aβ 的临床试验都没有成功。因此，针对这种复杂疾病的 Aβ 靶向治疗策略需要重新评估。在这篇综述中，我们分析了当前抗 Aβ 治疗策略所面临的挑战和关键点。除了 Aβ，tau 过度磷酸化、氧化应激和神经炎症等多种病理事件也参与 AD 的发病机制，并协同推动疾病进展，因此它们可能是 AD 治疗的重要靶点。由于 AD 的发病机制复杂且动态，需要采取三级预防策略来成功管理 AD。从大脑内外的系统性角度来解决疾病发病机制，以及针对危险因素和合并症的多领域干预，是 AD 治疗解决方案的重要方法。
