Triple Transgenic Model of Alzheimer's Disease

描述（改编自申请人的摘要）：美国国家研究院 老年痴呆症诊断的老化和里根研究所共识标准 疾病包括进行性痴呆的临床评估和 死后观察淀粉样斑块和神经纤维缠结， AD患者的大脑。患者的年龄是最大的风险， 存在AD，随后存在AD的一个或多个等位基因， 载脂蛋白E基因（APOE 4）在所有AD患者中约占45%。的 APOE 4的存在也与以下数量的增加有关： 神经纤维缠结和淀粉样蛋白斑块相比， 缺乏APOE 4等位基因。这些数据意味着斑块数量的增加， 缠结与阿尔茨海默氏痴呆症的增加有关。 显示进行性痴呆、淀粉样斑块和 神经纤维缠结是朝着开发一种安全， 治疗老年痴呆症的有效药物。根据报告的 在AD患者的研究中，动物模型也应该显示出增加的数量， 当APOE 4基因产物被激活时， 礼物 我们建议制作阿尔茨海默病的小鼠模型，以满足国家 老年研究所-里根研究所阿尔茨海默病标准。这 三重转基因小鼠（APP + TAU + APOE）被设计为同时显示 神经纤维缠结和淀粉样斑块。是一个准确 在人类AD模型中，我们假设神经元缠结的数量 在人APOE 4基因存在的情况下， 与人APOE 3基因产物相比。虽然只对斑块进行研究， 如果我们真的要开发一种老鼠， 阿尔茨海默病的模型，我们必须有进行性痴呆，斑块， 缠结。这种模式将有助于探索基本机制， 导致神经变性和痴呆症，在斑块，缠结和 apoE蛋白，因此，极大地促进了安全有效的 治疗阿尔茨海默氏症的药物

DESCRIPTION (Adapted from applicant's abstract): The National Institutes on Aging and Reagan Institute consensus criteria for the diagnosis of Alzheimer's disease includes a clinical evaluation of progressive dementia and a post-mortem observation of both amyloid plaques and neurofibrillary tangles in the brains of AD patients. Age of the patient is the largest risk for the presence of AD followed by the presence of one or more epsilon-4 alleles of the apolipoprotein-E gene (APOE4) in about 45 percent of all AD patients. The presence of APOE4 is also associated with an increase in the numbers of neurofibrillary tangles and amyloid plaques compared to those AD patients that lack APOE4 alleles. These data imply that increased numbers of plaques and tangles are associated with a gain of Alzheimer's dementia. An animal model that displays progressive dementia, amyloid plaques and neurofibrillary tangles is a critical step forward toward developing a safe and effective drug for the treatment of Alzheimer's disease. Based on reported studies of AD patients, an animal model should also display increased numbers of neurofibrillary tangles and amyloid plaques when APOE4 gene products are present. We propose to make a mouse model of Alzheimer's disease to meet the National Institute of Aging-Reagan Institute criteria for Alzheimer's disease. This triple transgenic mouse (APP + TAU + APOE) is designed to display both neurofibrilary tangles and amyloid plaques in their brains. To be an accurate model of human AD, we hypothesize that the numbers of neurofibrillary tangles and amyloid plaques should increase in the presence of human APOE4 gene products compared to human APOE3 gene products. Although work on plaque-only or tangle-only mice needs to continue, if we are really going to develop a mouse model of Alzheimer's disease, we must have progressive dementia, plaques, and tangles. Such a model would facilitate exploration of the basic mechanisms that cause neurodegeneration and dementia, in the 'presence of plaques, tangles and apoE proteins, and thus, greatly facilitate the finding of a safe and effective drug to block Alzheimer's dementia.