[阿尔茨海默病的抗淀粉样蛋白抗体疗法]。

Q3 Medicine Brain and Nerve Pub Date : 2024-10-01 DOI:10.11477/mf.1416202747
Moeko Shinohara, Kenjiro Ono
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引用次数: 0

摘要

阿尔茨海默病(AD)的病理特征是淀粉样蛋白斑块(由淀粉样β [Aβ]蛋白组成)和神经纤维缠结(由tau蛋白组成)的沉积以及神经元的死亡。Aβ 单体聚集形成低聚物、原纤维和成熟纤维。以前,成熟纤维和斑块被认为是神经毒性和神经退行性变的诱因。然而,越来越多的证据证明,低聚物和原纤维的毒性更强。最近的许多三期临床试验研究了抗Aβ抗体在AD中的作用,其中一些试验表明阿杜单抗、莱卡内单抗和多那单抗对这些患者有临床疗效。来卡尼单抗对原纤维的选择性高于纤维,而多那尼单抗只针对大脑特异性淀粉样斑块中的Aβ。相比之下,其他抗Aβ抗体对AD没有疗效。
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[Anti-Amyloid Antibody Therapy for Alzheimer's Disease].

Alzheimer's disease (AD) is pathologically characterized by deposition of amyloid plaques (comprising amyloid β [Aβ] protein) and neurofibrillary tangles (comprising tau protein), and neuronal death. Aβ monomers aggregate to form oligomers, protofibrils, and mature fibrils. Previously, the mature fibrils and plaques were implicated as contributors to neurotoxicity and neurodegeneration. However, a growing body of evidence proves stronger toxicity of oligomers and protofibrils. Among the many recent phase 3 clinical trials that have investigated the role of anti-Aβ antibodies in AD, some have shown the clinical efficacy of aducanumab, lecanemab, and donanemab in these patients. Lecanemab showed selectivity towards protofibrils over fibrils, and donanemab was specifically directed against Aβ only in brain-specific amyloid plaques. In contrast, other anti-Aβ antibodies did not show efficacy in AD.

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Brain and Nerve
Brain and Nerve Medicine-Neurology (clinical)
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