Hara Hideo, Inoue Makoto, Adachi Kayo, Yonemitsu Yoshikazu, Hasegawa Mamoru, Nabeshima Toshitaka, Tabira Takeshi
Department of Vascular Dementia Research, NILS, National Center for Geriatrics and Gerontology, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2007 Apr;27(2):53-6.
Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-l (Al) deposits in the central nervous system. Based on the amyloid cascade theory, many reports indicated that immunotherapy is effective for the treatment of Alzheimer's disease. We developed a mucosal immunotherapy for Alzheimer's disease via oral vaccine with recombinant adeno-associated virus (AAV) vector and nasal administration of recombinant sendaivirus vector expressing Al 1-43/IL-10. Oral or nasal administration of recombinant virus vector induced the long-term expression of All in the epithelial cells and presented the Ap antigen to the mucosal immune system. Antibody levels in the mouse serum were elevated after 4 weeks and the antibody inhibited the aggregation of Ap in vitro. Immunohistochemistry of the APP transgenic mouse brain tissue showed that All burdens were markedly decreased in the treated mouse compared to the control. The inflammation was not recognized in any organ including brain and kidney. Mucosal immunotherapy with viral vectors significantly cleared the Ap depositions without inflammation and reduced the levels of Al in the brain homogenates of APP transgenic mice; therefore, it might be effective for the treatment of Alzheimer's disease.
阿尔茨海默病的特征是由于中枢神经系统中淀粉样蛋白-β（Aβ）沉积导致认知功能进行性丧失。基于淀粉样蛋白级联反应理论，许多报告表明免疫疗法对阿尔茨海默病的治疗有效。我们通过用重组腺相关病毒（AAV）载体的口服疫苗和鼻内给予表达Aβ1-43/IL-10的重组仙台病毒载体，开发了一种用于阿尔茨海默病的黏膜免疫疗法。口服或鼻内给予重组病毒载体诱导Aβ在上皮细胞中的长期表达，并将Aβ抗原呈递给黏膜免疫系统。4周后小鼠血清中的抗体水平升高，且该抗体在体外抑制Aβ的聚集。APP转基因小鼠脑组织的免疫组织化学显示，与对照组相比，治疗组小鼠的Aβ负荷明显降低。在包括脑和肾在内的任何器官中均未发现炎症。用病毒载体进行的黏膜免疫疗法显著清除了Aβ沉积且无炎症反应，并降低了APP转基因小鼠脑匀浆中Aβ的水平；因此，它可能对阿尔茨海默病的治疗有效。
