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

Amyloid-beta (A beta) 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 A beta-targeted clinical trials have not succeeded. Therefore, the A beta-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-A beta therapeutic strategies. In addition to A beta, 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.

Automated summary

The therapeutic strategy for Alzheimer's disease needs to be re-evaluated, with a focus on not only targeting amyloid-beta, but also other important pathological events as treatment targets. Tertiary prevention strategies are necessary for successful management of the complex and dynamic pathogenesis of Alzheimer's disease.