Tamura Yuichi, Hamajima Kenji, Matsui Kiyohiko, Yanoma Shunsuke, Narita Masato, Tajima Nobuyoshii, Xin Ke-Qin, Klinman Dennis, Okuda Kenji
Nichiiko Pharmaceutical, Co., Ltd, Toyama, Japan.
Neurobiol Dis. 2005 Nov;20(2):541-9. doi: 10.1016/j.nbd.2005.04.007.
This work examines whether administering the F(ab' )2 fragment of an IgG1 monoclonal antibody (mAb) targeting the N-terminal 1-13 amino acids of the beta-amyloid peptide (Abeta mAb) reduces amyloid deposition in Alzheimer's disease (AD). The F(ab')2 fragment was injected intraperitoneally or intracranially into Tg2576 mice, a murine model of human AD. Both routes of administration significantly reduced Abeta plaque formation in the brain, as determined immunohistochemically and by monitoring levels of Abeta1-40 and Abeta1-42 peptide. Use of the F(ab')2 fragment significantly reduced phagocytic infiltration in the CNS when compared to intact mAb. Since IgG1 Abs do not fix complement, these findings suggest that effective in vivo clearance of amyloid deposits can be achieved without stimulation of FcR-reactive phagocytes or activation of the complement cascade.
这项研究考察了给予靶向β-淀粉样肽N端1 - 13个氨基酸的IgG1单克隆抗体（mAb）的F(ab')2片段是否能减少阿尔茨海默病（AD）中的淀粉样蛋白沉积。将F(ab')2片段腹腔内或颅内注射到Tg2576小鼠（一种人类AD的小鼠模型）体内。通过免疫组织化学以及监测β-淀粉样蛋白1 - 40和β-淀粉样蛋白1 - 42肽的水平测定，两种给药途径均显著减少了大脑中的β-淀粉样蛋白斑块形成。与完整的mAb相比，使用F(ab')2片段显著减少了中枢神经系统中的吞噬细胞浸润。由于IgG1抗体不固定补体，这些发现表明，无需刺激FcR反应性吞噬细胞或激活补体级联反应，就能在体内有效清除淀粉样蛋白沉积物。
