Tampellini Davide, Magrané Jordi, Takahashi Reisuke H, Li Feng, Lin Michael T, Almeida Cláudia G, Gouras Gunnar K
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
J Biol Chem. 2007 Jun 29;282(26):18895-906. doi: 10.1074/jbc.M700373200. Epub 2007 Apr 27.
Immunotherapy against beta-amyloid peptide (Abeta) is a leading therapeutic direction for Alzheimer disease (AD). Experimental studies in transgenic mouse models of AD have demonstrated that Abeta immunization reduces Abeta plaque pathology and improves cognitive function. However, the biological mechanisms by which Abeta antibodies reduce amyloid accumulation in the brain remain unclear. We provide evidence that treatment of AD mutant neuroblastoma cells or primary neurons with Abeta antibodies decreases levels of intracellular Abeta. Antibody-mediated reduction in cellular Abeta appears to require that the antibody binds to the extracellular Abeta domain of the amyloid precursor protein (APP) and be internalized. In addition, treatment with Abeta antibodies protects against synaptic alterations that occur in APP mutant neurons.
针对β-淀粉样肽（Aβ）的免疫疗法是阿尔茨海默病（AD）的主要治疗方向。在AD转基因小鼠模型中的实验研究表明，Aβ免疫可减少Aβ斑块病理并改善认知功能。然而，Aβ抗体减少大脑中淀粉样蛋白积累的生物学机制仍不清楚。我们提供的证据表明，用Aβ抗体处理AD突变神经母细胞瘤细胞或原代神经元可降低细胞内Aβ水平。抗体介导的细胞内Aβ减少似乎需要抗体与淀粉样前体蛋白（APP）的细胞外Aβ结构域结合并内化。此外，用Aβ抗体治疗可防止APP突变神经元中发生的突触改变。
