Iron Metabolism Alterations in Alzheimer's Disease

阿尔茨海默病中铁代谢的改变

• 批准号: 6908117
• 负责人: WOLFF M. KIRSCH
• 金额: $ 130.75万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6908117
• 关键词: Alzheimer' s disease; amyloid proteins; bioimaging /biomedical imaging; biomarker; brain mapping; brain metabolism; clinical research; cognition disorders; disease /disorder proneness /risk; flow cytometry; genetic polymorphism; genetically modified animals; human middle age (35-64); human old age (65+); human subject; immunocytochemistry; iron metabolism; laboratory mouse; lymphocyte; magnetic resonance imaging; oxidative stress; psychometrics; technology /technique development

DESCRIPTION (provided by applicant): The institution directing this Bioengineering Research Partnership is the Loma Linda University (Neurosurgery Center for Research, Training and Education, Departments of Molecular Biology and Molecular Genetics, Biochemistry, Radiology, Radiobiology, Internal Medicine, Psychiatry and Pathology). Partners include BioErgonomics, Inc., St Paul, MN and the MRI Institute for Biomedical Research, St. Louis, MO. The goal of our multidisciplinary Bioengineering Research Partnership is to define the role of altered brain iron metabolism as a risk factor for Alzheimer's Disease in the in the context of elderly MCI patients. The engineering focus of the study is: (I) defining ex vivo markers in peripheral blood cells indicating iron or amyloid perturbations and (2) the development of a new magnetic resonance imaging (MRI) technology to quantitate and differentiate brain iron. Study subjects will be 75 patients (50 years of age or older) with minimal cognitive impairment who will be followed longitudinally for a three to four year period with sequential psychometric tests, special MRI sequences, and peripheral blood cell studies. Control subjects will consist of 25 healthy age-matched individuals who will be subjected to the same tests as the MCI group. A genetically engineered mouse with an iron regulatory protein 2 "knockout" that accumulates abnormal quantities of brain iron and displays a neurodegenerative disorder will be used to validate our new technology. A search for polymorphisms in the IRP-2 gene will be part of each patient's evaluation. At four years of serial follow-up it is anticipated that about 15% of the 75 study subjects will have AD, and correlations of psychometric data, brain iron localization and quantitation, as well as immunocytochemical peripheral blood will be established using statistical consultation and autopsy information if available.

描述（由申请人提供）：指导这种生物工程研究伙伴关系的机构是Loma Linda大学（神经外科研究，培训和教育中心，分子生物学和分子遗传学，生物化学，放射学，放射生物学，内科医学，精神病学和病理学）。合作伙伴包括MN的Bioergonomics，Inc。，St Paul和MRI生物医学研究所，密苏里州圣路易斯。我们多学科生物工程研究伙伴关系的目的是将改变脑铁代谢的作用定义为老年MCI患者的阿尔茨海默氏病的危险因素。该研究的工程重点是：（i）在表明铁或淀粉样蛋白扰动的外周血细胞中定义离体标记，以及（2）开发新的磁共振成像（MRI）技术，以定量和区分脑铁。研究受试者将是75名患者（50岁以上），认知障碍最小，他们将在三到四年内进行纵向跟踪，并进行顺序心理测试，特殊的MRI序列和外周血细胞研究。对照受试者将由25个健康年龄匹配的人组成，他们将接受与MCI组相同的测试。具有铁调节蛋白2“基因敲除”的基因工程小鼠会积聚异常的脑铁并显示神经退行性障碍，以验证我们的新技术。在IRP-2基因中寻找多态性的搜索将是每个患者评估的一部分。在四年的串行随访中，预计在75名研究受试者中，约有15％将具有AD，心理测量数据，脑铁定位和定量的相关性以及免疫细胞化学外周血将使用统计咨询和尸检信息（如果有）建立。