THE DISTRIBUTION OF FE, CU AND ZN IN A ALZHEIMER?S DISEASE MICE MODEL

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 人β-淀粉样前体蛋白（APP）转基因（Tg）小鼠是一种成熟的模型 治疗阿尔茨海默病它广泛用于病理学研究、诱变实验和 筛选治疗剂。在大脑中具有高β淀粉样蛋白水平的APP Tg小鼠显示 突触丧失、行为改变和突触传递缺陷。最近，参与 氧化还原活性金属在阿尔茨海默病的病理学中的作用已经被确定。我们 假设Tg小鼠中APP过表达影响金属稳态， 从而影响金属在脑内的分布。微焦点X射线荧光成像是最好的 人APP Tg小鼠海马内Fe、Cu、Zn分布的可视化技术 和健康（非转基因）对照。我们预计会检测到铜和锌浓度的增加 在斑块中。将在斑块和健康组织上尝试Cu和Fe micro-XANES以监测 金属氧化态的可能差异。在小鼠模型上的工作 与对阿尔茨海默氏症患者的脑组织进行死后分析相比，它允许 干扰程度高，如在不同时间点监测病情 在不同治疗剂给药期间或由于 特定的突变在这个提案中，我们将分析两个不同年龄的小鼠大脑： 在斑块形成前后。拟议的研究将有助于揭示参与 金属离子在阿尔茨海默病发病中的作用

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human beta-amyloid precursor protein (APP) transgenic (Tg) mice is a well established model for Alzheimer's disease. It is widely used for pathology studies, mutagenesis experiments and screening of therapeutic agents. APP Tg mice with high beta-amyloid levels in the brain show synapse loss, behavioral changes, and synaptic transmission deficit. Recently, involvement of the redox active metals in the pathology of Alzheimer's disease has been identified. We hypothesize that overexpression of APP in Tg mice is affecting the metal homeostasis and, thus, the metal distributions in brain. Micro-focus X-ray fluorescent imaging is the best technique to visualize the Fe, Cu, Zn distributions in the hippocampus of human APP Tg mice and healthy (non transgenic) control. We expect to detect increased Cu and Zn concentrations in plaques. Cu and Fe micro-XANES will be attempted on plaques and healthy tissues to monitor possible differences in the metal oxidation states. Work on the mice model has enormous advantages compared to postmortem analysis of brain tissues of Alzheimer's patients. It allows a high degree of interference, such as monitoring at different points in time as the disease progresses, during administration of different therapeutic agents or as a consequence of specific mutations. In this proposal we will analyze brains of mice at two different ages: before and after plaques formation. The proposed study will help to uncover the involvement of metal ions in the onset of Alzheimer's disease.