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

作　　者：Bin-Lu Sun Yang Chen Dong-Yu Fan Chi Zhu Fan Zeng Yan-Jiang Wang 

机构地区：[1]Department of Neurology and Center for Clinical Neuroscience,Daping Hospital,Third Military Medical University,Chongqing 400042,China [2]Chongqing Key Laboratory of Ageing and Brain Diseases,Chongqing 400042,China [3]Institute of Brain and Intelligence,Third Military Medical University,Chongqing 400042,China

出　　处：《Science China(Life Sciences)》2021年第6期926-937,共12页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(91749206,81930028,81625007,81870860,31921003)。

摘　　要：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-Aβtherapeutic 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.

关 键 词：Alzheimer's disease amyloidβ immunotherapy Β-SECRETASE Γ-SECRETASE enzyme inhibitor multi-target therapy tertiary prevention strategy 

分 类 号：R749.16[医药卫生—神经病学与精神病学]