FUNCTIONAL CONSEQUENCES OF VACCINATION IN AD TG MICE

描述(改编自《调查者摘要》)：接种疫苗是唯一 曾经根除疾病的预防性或治疗性干预 (如天花)。它在疾病治疗中也有很好的实用性(例如 狂犬病)。阿尔茨海默病(AD)转基因小鼠模型发展迅速 大脑皮层和海马区A-β密度沉积，神经元性改变 最终，对这些沉积物的炎症反应。最近， PDAPP转基因小鼠接种A-β多肽后， 防止A-β蛋白在大脑中沉积。不幸的是，功能性的 这种治疗的后果不能在这些小鼠身上有效地评估， 由于在早期观察到严重的学习和记忆缺陷 寿命。调查人员建议评估以下各项的功能后果 在他们的双转基因Mapp/Mps1-AD小鼠模型中接种疫苗。这些老鼠 发展学习和记忆缺陷，这与积累 A-β，存款。他们将测试预防/减少A-β病毒的疫苗 积累可以减弱或加重在脑部发现的行为缺陷 这些老鼠。他们根据年龄的不同预测不同的结果 接种疫苗。他们将从组织病理学和生化方面证实 疫苗减少了中枢神经系统中的A-β负荷，同时仔细记录了程度 在这些小鼠身上发现的炎症。除了测试疫苗接种 假设，这些数据将解决A-β淀粉样蛋白在 认知功能障碍。在很小的时候就预料到预防性接种 将改善一些通常发生在这些人的行为缺陷 老鼠，他们将研究A-Beta1-42肽的替代品作为疫苗， 并在老年和幼龄小鼠身上测试它们的有效性。便宜一点的 多肽的替代品是DNA疫苗，这是一种新的接种技术，它 能引起体液免疫和细胞免疫。这项技术已经在人类身上了 临床试验。多克隆抗体和单抗的被动免疫 制剂是疫苗的替代品，将在 这个动物模型。被动免疫的优点是安全和 免疫效果差的老年人有可能获得更好的效果 对疫苗的反应。加在一起，这些后续研究将确定 体液免疫反应和细胞免疫反应在调节中的相对贡献 疫苗在转基因AD小鼠模型中的作用。

DESCRIPTION (Adapted from the Investigator's Abstract): Vaccination is the only prophylactic or therapeutic intervention that has ever eliminated a disease (e.g. smallpox). It also has well established utility in disease therapy (e.g. rabies). Transgenic mouse models of Alzheimer's disease (AD) develop high density A-beta deposits in cerebral cortex and hippocampus, neuritic changes and, ultimately, inflammatory reactions to these deposits. Recently, vaccination of the PDAPP transgenic mouse with A-beta peptide was found to prevent A-beta deposition in the brain. Unfortunately, the functional consequences of this treatment could not be effectively assessed in these mice, owing to severe learning and memory deficiencies observed early in the lifespan. The investigators propose to assess the functional consequences of vaccination in their doubly transgenic mAPP/mPS1 -mouse model of AD. These mice develop learning and memory deficits which correlate with the accumulation of A-beta, deposits. They will test whether vaccines that prevents/reduces A-beta accumulation can either attenuate or aggravate the behavioral deficits found in these mice. They predict different outcomes depending on the age of vaccination. They will verify histopathologically and biochemically that the vaccines reduce A-beta loads in the CNS, while carefully documenting the degree of inflammation found in these mice. In addition to testing the vaccination hypothesis, these data will address the question of A-beta amyloid's role in cognitive dysfunction. Anticipating that prophylactic vaccination at early ages will ameliorate some of the behavioral deficits normally occurring in these mice, they'll investigate alternatives to the A-beta1-42 peptide as vaccines, and test their effectiveness in old as well as young mice. One less expensive alterative to peptides are DNA vaccines, a novel inoculation technique which elicits both humoral and cellular immunity. This technology is already in human clinical trials. Passive immunization with polyclonal and monoclonal antibody preparations is an alterative to vaccines that will be tested for efficacy in this animal model. Advantages of passive immunization are safety and potentially greater effectiveness in older individuals with poor immunization responses to vaccines. Together, these later studies will determine the relative contributions of humoral and cellular immune reactions in mediating the effects of vaccines in transgenic mouse models of AD.