FUNCTIOINAL CONSEQUENCES OF VACCINATION IN AD TG MICE

描述（改编自研究者摘要）：疫苗接种是唯一 预防性或治疗性干预，曾经消除了疾病 (e.g.天花）。它在疾病治疗中也具有良好的实用性（例如， 狂犬病）。阿尔茨海默病（AD）的转基因小鼠模型发展迅速， 大脑皮层和海马中密度A-β沉积，神经炎性改变 并最终对这些沉积物产生炎症反应。最近， 发现用A-β肽接种PDAPP转基因小鼠， 防止A β在大脑中沉积不幸的是， 在这些小鼠中不能有效地评估这种治疗的结果， 由于早期观察到的严重学习和记忆缺陷， 寿命研究人员建议评估以下功能性后果： 在其AD的双转基因mAPP/mPS 1小鼠模型中接种。这些小鼠 发展与积累相关的学习和记忆缺陷， A-β，存款。他们将测试预防/减少A β的疫苗是否 积累可以减轻或加重行为缺陷， 这些老鼠他们根据年龄的不同预测不同的结果。 预防针他们将从组织病理学和生物化学方面证实， 疫苗降低了CNS中的A-β负荷，同时仔细记录了 在这些老鼠身上发现的炎症。除了测试疫苗外 假设，这些数据将解决的问题，A-β淀粉样蛋白的作用， 认知功能障碍预计在早期接种预防性疫苗 将改善一些行为缺陷通常发生在这些 他们将研究A-β 1 -42肽作为疫苗的替代品， 并在年老和年轻的老鼠身上测试它们的有效性。便宜一点 肽的替代物是DNA疫苗，一种新的接种技术， 增强体液免疫和细胞免疫。这项技术已经在人类 临床试验用多克隆和单克隆抗体进行被动免疫 疫苗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， 对免疫力差的老年人可能更有效 对疫苗的反应。总之，这些后来的研究将决定 体液和细胞免疫反应在介导 疫苗在AD转基因小鼠模型中的作用。

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.