Amyloid-β in Alzheimer's disease: Structure, toxicity, distribution, treatment, and prospects

Ibrain Pub Date : 2024-05-23 DOI:10.1002/ibra.12155
Yifan Yu, Shilong Yu, Giuseppe Battaglia, Xiaohe Tian
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引用次数: 0

Abstract

Amyloid-β (Aβ) is a pivotal biomarker in Alzheimer's disease (AD), attracting considerable attention from numerous researchers. There is uncertainty regarding whether clearing Aβ is beneficial or harmful to cognitive function. This question has been a central topic of research, especially given the lack of success in developing Aβ-targeted drugs for AD. However, with the Food and Drug Administration's approval of Lecanemab as the first anti-Aβ medication in July 2023, there is a significant shift in perspective on the potential of Aβ as a therapeutic target for AD. In light of this advancement, this review aims to illustrate and consolidate the molecular structural attributes and pathological ramifications of Aβ. Furthermore, it elucidates the determinants influencing its expression levels while delineating the gamut of extant Aβ-targeted pharmacotherapies that have been subjected to clinical or preclinical evaluation. Subsequently, a comprehensive analysis is presented, dissecting the research landscape of Aβ across the domains above, culminating in the presentation of informed perspectives. Concluding reflections contemplate the supplementary advantages conferred by nanoparticle constructs, conceptualized within the framework of multivalent theory, within the milieu of AD diagnosis and therapeutic intervention, supplementing conventional modalities.

Abstract Image

阿尔茨海默病中的淀粉样蛋白-β:结构、毒性、分布、治疗和前景
淀粉样蛋白-β(Aβ)是阿尔茨海默病(AD)的关键生物标志物,引起了众多研究人员的极大关注。目前还不确定清除 Aβ 对认知功能是有益还是有害。这个问题一直是研究的中心议题,尤其是考虑到在开发针对阿兹海默症的 Aβ 靶向药物方面缺乏成功经验。然而,随着美国食品和药物管理局于 2023 年 7 月批准莱卡单抗作为首个抗 Aβ 药物,人们对 Aβ 作为 AD 治疗靶点的潜力的看法发生了重大转变。鉴于这一进展,本综述旨在说明和巩固 Aβ 的分子结构属性和病理影响。此外,它还阐明了影响其表达水平的决定性因素,同时划分了已接受临床或临床前评估的现有 Aβ 靶向药物疗法的范围。随后,报告进行了全面分析,剖析了上述领域的 Aβ 研究情况,并最终提出了有理有据的观点。最后,在多价理论的框架下,考虑了纳米粒子结构在AD诊断和治疗干预中的补充优势,并对传统模式进行了补充。
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CiteScore
0.90
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