Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development.
Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development.
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发表时间：
2003
影响因子：
3.5
通讯作者：
A. Nath;Elizabeth Hall;Marnia Tuzova;Michael R. Dobbs;Melina Jons;C. Anderson;J. Woodward;Zhihong Guo;Weiming Fu;R. Kryscio;D. Wekstein;Charles D. Smith;W. Markesbery;M. Mattson
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作者：
A. Nath;Elizabeth Hall;Marnia Tuzova;Michael R. Dobbs;Melina Jons;C. Anderson;J. Woodward;Zhihong Guo;Weiming Fu;R. Kryscio;D. Wekstein;Charles D. Smith;W. Markesbery;M. Mattson
对淀粉样前体蛋白转基因小鼠的研究表明，对淀粉样β蛋白(Abeta)的免疫反应可能有助于消除大脑中的斑块，但由于一些患者出现严重的神经系统并发症，Abeta疫苗在阿尔茨海默病(AD)患者中的初步临床试验被叫停。我们现在提供的证据表明，AD患者对Abeta的免疫反应增强，与预期相反，Abeta抗体增强了多肽的神经毒性活性。AD患者血清中Abeta抗体滴度显著升高，Abeta抗体与脑内淀粉样斑块相关，但患者中没有证据表明对Abeta的细胞免疫反应。在老年APP突变转基因小鼠的血清中检测到Abeta抗体，但在年轻转基因或非转基因小鼠的血清中未检测到Abeta抗体。APP突变小鼠的血清增强了Abeta的神经毒性。我们的数据表明，AD患者对Abeta的体液免疫反应可能会促进神经元退化，这一过程对基于疫苗的AD治疗的未来具有重要意义。
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.