神经毒性
免疫系统
转基因小鼠
自身抗体
免疫学
抗体
淀粉样蛋白(真菌学)
发病机制
淀粉样前体蛋白
医学
阿尔茨海默病
β淀粉样蛋白
转基因
神经学
疾病
生物
内科学
病理
毒性
生物化学
基因
精神科
作者
Avindra Nath,Elizabeth Hall,Marnia Tuzova,Michael Dobbs,M. D. Jones,Caroline F. Anderson,Jerold G. Woodward,Zhihong Guo,Weiming Fu,Richard J. Kryscio,David R. Wekstein,Charles B. Smith,William R. Markesbery,Mark P. Mattson
摘要
Studies of amyloid precursor protein transgenic mice suggest that immune responses to amyloid beta peptide (Abeta) may be instrumental in the removal of plaques from the brain, but the initial clinical trial of an Abeta vaccine in patients with Alzheimer s disease (AD) was halted as the result of serious neurological complications in some patients. We now provide evidence that AD patients exhibit an enhanced immune response to Abeta and that, contrary to expectations, Abeta antibodies enhance the neurotoxic activity of the peptide. Serum titers to Abeta were significantly elevated in AD patients and Abeta antibodies were found in association with amyloid plaques in their brains, but there was no evidence of cell-mediated immune responses to Abeta in the patients. Abeta antibodies were detected in the serum of old APP mutant transgenic mice with plaque-like Abeta deposits, but not in the serum of younger transgenic or nontransgenic mice. Serum from APP mutant mice potentiated the neurotoxicity of Abeta. Our data suggest that a humoral immune response to Abeta in AD patients may promote neuronal degeneration, a process with important implications for the future of vaccine-based therapies for AD.
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