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Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives

机译：对淀粉样蛋白β靶向治疗的批判性思考：挑战和观点

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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.
机译：淀粉样蛋白β（Aβ）在阿尔茨海默病（AD）的发病机制中起着枢轴作用，并且被认为是AD的主要治疗靶标。然而，大多数Aβ针对性的临床试验没有成功。因此，需要重新评估治疗这种复杂疾病的Aβ靶向治疗策略。在本综述中，我们分析了目前抗Aβ治疗策略的挑战和关键点。除了Aβ，诸如Tau超磷酸化，氧化应激和神经炎症的多种病理事件以及参与AD发病机制和协同促进疾病进展，可能是AD治疗的重要靶标。由于其复杂和动态发病机制，AD的成功管理需要第三次预防策略。全身观点解决大脑内外疾病发病机制，以及靶向危险因素和合并症的多畴干预，是广告治疗溶液的重要方法。

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