Targeting amyloid-β in Alzheimer’s disease: A critical analysis of clinical trials and their implications for drug development
نویسندگان
1 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
2 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
3 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
4 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
5 Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan Province, China
6 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
7 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
8 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
9 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China
doi
10.22038/ijbms.2026.92189.19902چکیده
Alzheimer’s disease (AD), a prevalent neurodegenerative dementia, is characterized by amyloid-β (Aβ) plaques and neurofibrillary tangles, with Aβ playing a central pathogenic role. Approved AD drugs, primarily acetylcholinesterase inhibitors, only alleviate symptoms without modifying disease progression. Aβ-targeting strategies aim to inhibit Aβ production or enhance its clearance, leveraging early deposition for proactive intervention. Preclinical studies show Aβ reduction mitigates neurodegeneration, but clinical trials reveal challenges: γ-secretase inhibitors face off-target toxicities and limited efficacy, while BACE1 inhibitors suffer from safety issues or failure to improve cognition. Despite setbacks, advancing understanding of AD pathogenesis and optimized drug design/ trial protocols sustain the potential of Aβ-targeted therapies. This review aims to advance Aβ-targeted therapies for AD by integrating lessons from prior clinical trials and outlining strategic directions for future research and development.
