Münch G, Robinson S R
Neuroimmunological Cell Biology Unit, Interdisciplinary Centre for Clinical Research (IZKF), University of Leipzig, Johannisallee 30 a, D-04103 Leipzig, Federal Republic of Germany.
J Neural Transm (Vienna). 2002 Jul;109(7-8):1081-7. doi: 10.1007/s007020200091.
Studies in transgenic mouse models of Alzheimer's disease suggested the development of a vaccine that would induce the production of antibodies against amyloid-beta (Abeta) peptide, which in turn would stimulate microglia to phagocytose and remove senile plaques. However, some patients in the human clinical trials developed symptoms of brain inflammation, demonstrated by lymphocyte infiltration and elevated protein levels. These parameters are indicative of a breakdown of the blood-brain-barrier and entry of T-cells into the brain. Abeta-specific activated T-helper cells have the potential to amplify the existing pro-inflammatory conditions that are present in the brains of Alzheimer's disease patients. Cytotoxic T-cells might even attack the amyloid precursor protein which is present on the surface of many cells, including neurons. Before undertaking further vaccination trials there is a need to re-assess the risks associated with Abeta vaccination and with the therapeutic containment of a neuroinflammatory response. These risks may not be justified in the light of recent studies which have shown the efficacy of conventional, low-risk treatments in slowing the progress of AD.
对阿尔茨海默病转基因小鼠模型的研究表明，可以研发一种疫苗来诱导产生针对β淀粉样蛋白（Aβ）肽的抗体，进而刺激小胶质细胞吞噬并清除老年斑。然而，一些参与人体临床试验的患者出现了脑部炎症症状，表现为淋巴细胞浸润和蛋白质水平升高。这些指标表明血脑屏障遭到破坏，T细胞进入大脑。Aβ特异性活化的辅助性T细胞有可能加剧阿尔茨海默病患者大脑中现有的促炎状态。细胞毒性T细胞甚至可能攻击许多细胞（包括神经元）表面存在的淀粉样前体蛋白。在进行进一步的疫苗试验之前，有必要重新评估与Aβ疫苗接种以及神经炎症反应的治疗控制相关的风险。鉴于最近的研究表明传统的低风险治疗方法在减缓阿尔茨海默病进展方面的有效性，这些风险可能并不合理。
