Aducanumab is a humanized IgG1 monoclonal antibody that specifically targets amyloid β (Aβ) aggregates, including soluble oligomers and fibrillar plaques[1]. Aducanumab reduces the amyloid burden in the brains of patients with Alzheimer's disease (AD) by binding to the N-terminal epitope of Aβ and promoting microglia-mediated plaque clearance[2]. Aducanumab is the first antibody approved for the treatment of AD[3]. Aducanumab interacts weakly with Aβ monomers[4].
In vivo, Aducanumab (10mg/kg) was treated intraperitoneally in TgAPPPS1-21 mice for 4 months, which significantly reduced the number of senile plaques in the mouse hippocampus[5]. Aducanumab (3mg/kg) was treated intravenously in 5×FAD mice, which significantly reduced the number of senile plaques in the mouse hippocampus, increased the number of astrocytes, and alleviated cognitive deficits[6].
References:
[1] Sevigny J, Chiao P, Bussière T, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease[J]. Nature, 2016, 537(7618): 50-56.
[2] Kim B H, Kim S, Nam Y, et al. Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives[J]. Translational Neurodegeneration, 2025, 14(1): 6.
[3] Mukhopadhyay S, Banerjee D. A primer on the evolution of aducanumab: the first antibody approved for treatment of Alzheimer’s disease[J]. Journal of Alzheimer's Disease, 2021, 83(4): 1537-1552.
[4] Arndt J W, Qian F, Smith B A, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β[J]. Scientific reports, 2018, 8(1): 6412.
[5] Bastrup J, Hansen K H, Poulsen T B G, et al. Anti-Aβ antibody aducanumab regulates the proteome of senile plaques and closely surrounding tissue in a transgenic mouse model of Alzheimer’s disease[J]. Journal of Alzheimer's Disease, 2021, 79(1): 249-265.
[6] Kong C, Yang E J, Shin J, et al. Enhanced delivery of a low dose of aducanumab via FUS in 5× FAD mice, an AD model[J]. Translational Neurodegeneration, 2022, 11(1): 57.
Aducanumab是一种人源化IgG1单克隆抗体，特异性靶向β-淀粉样蛋白（Aβ）聚集体，包括可溶性寡聚体和纤维状斑块[1]。Aducanumab通过结合Aβ的N端表位，促进小胶质细胞介导的斑块清除，从而减少阿尔茨海默病（AD）患者大脑中的淀粉样蛋白负荷[2]。Aducanumab是第一个被批准用于治疗阿尔茨海默病的抗体[3]。Aducanumab与Aβ单体的相互作用较弱[4]。
在体内，Aducanumab（10mg/kg）通过腹腔注射治疗TgAPPPS1-21小鼠4个月，显著减少了小鼠海马中老年斑数量[5]。Aducanumab（3mg/kg）通过静脉注射治疗5×FAD小鼠，显著减少了小鼠海马中老年斑数量，增加了星形胶质细胞数量，减轻了认知功能缺陷[6]。