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

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Abstract

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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (91749206, 81930028, 81625007, 81870860, 31921003).

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  1. Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

    Bin-lu Sun, Yang Chen, Dong-yu Fan, Chi Zhu, Fan Zeng & Yan-jiang Wang

  2. Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China

    Bin-lu Sun, Yang Chen, Dong-yu Fan, Chi Zhu, Fan Zeng & Yan-jiang Wang

  3. Institute of Brain and Intelligence, Third Military Medical University, Chongqing, 400042, China

    Bin-lu Sun, Yang Chen, Dong-yu Fan, Chi Zhu, Fan Zeng & Yan-jiang Wang

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Sun, Bl., Chen, Y., Fan, Dy. et al. Critical thinking on amyloid-beta-targeted therapy: challenges and perspectives. Sci. China Life Sci. 64, 926–937 (2021). https://doi.org/10.1007/s11427-020-1810-y

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