Shinohara Moeko, Ono Kenjiro
Department of Neurology, Kanazawa University Graduate School of Medical Sciences.
Brain Nerve. 2024 Oct;76(10):1119-1125. doi: 10.11477/mf.1416202747.
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.
阿尔茨海默病（AD）的病理特征是淀粉样斑块（由淀粉样β蛋白[Aβ]组成）和神经原纤维缠结（由tau蛋白组成）的沉积以及神经元死亡。Aβ单体聚集形成寡聚体、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促成因素。然而，越来越多的证据证明寡聚体和原纤维具有更强的毒性。在最近许多研究抗Aβ抗体在AD中作用的3期临床试验中，一些试验显示了阿杜卡努单抗、莱卡努单抗和多纳努单抗对这些患者的临床疗效。莱卡努单抗对原纤维的选择性高于纤维，而多纳努单抗仅针对脑特异性淀粉样斑块中的Aβ。相比之下，其他抗Aβ抗体在AD中未显示出疗效。
