Triple Transgenic Model of Alzheimer's Disease

描述(改编自申请者摘要)：美国国立卫生研究院 老龄化和里根研究所对阿尔茨海默氏症诊断的共识标准 疾病包括进行性痴呆症的临床评估和 大鼠脑淀粉样斑块和神经原纤维缠结的尸检观察 阿尔茨海默病患者的大脑。患者的年龄是最大的风险 AD的存在伴随着一个或多个epsilon-4等位基因的存在 约45%的AD患者存在载脂蛋白-E基因(APOE4)。这个 APOE4的存在也与Apo4的数量增加有关 神经原纤维缠结和淀粉样斑块与AD患者的比较 缺乏载脂蛋白4等位基因。这些数据意味着斑块和斑块数量的增加 纠缠与阿尔茨海默氏症的增加有关。 一种显示进行性痴呆、淀粉样斑块和 神经原纤维缠绕是朝着开发一种安全和 治疗阿尔茨海默病的有效药物。基于已报告的 对AD患者的研究，动物模型也应该显示出增加的数量 当APOE4基因产物 现在时。 我们建议制作一种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的标准。这 三重转基因小鼠(APP+TAU+APOE)被设计为同时显示两者 他们大脑中的神经纤维缠结和淀粉样斑块。准确地说， 在人类AD模型中，我们假设神经原纤维缠结的数量 在人类APOE4基因的存在下，淀粉样斑块应该增加 与人类载脂蛋白3基因产物进行比较。尽管仅针对斑块的工作或 如果我们真的要开发一种老鼠，只有缠绕的老鼠需要继续下去 阿尔茨海默病的模型，我们必须有进行性痴呆，斑块，和 唐格斯。这样的模式将有助于探索以下基本机制： 导致神经变性和痴呆症，在斑块、缠结和 APOE蛋白，从而极大地方便了寻找安全有效的 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.