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(由申请者提供)：指导这一生物工程研究伙伴关系的机构是洛玛琳达大学(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、精神病学和病理学)。合作伙伴包括明尼苏达州圣保罗的生物人体工程学公司和密苏里州圣路易斯的核磁共振生物医学研究所。我们多学科生物工程研究伙伴关系的目标是确定脑铁代谢改变在老年MCI患者中作为阿尔茨海默病风险因素的作用。这项研究的工程重点是：(I)在外周血细胞中定义指示铁或淀粉样蛋白扰动的体外标志物，以及(2)开发一种新的磁共振成像(MRI)技术来定量和区分脑铁。研究对象将是75名轻度认知障碍的患者(50岁或以上)，他们将接受为期三到四年的纵向跟踪，进行连续的心理测量测试、特殊的MRI序列和外周血细胞检查。对照受试者将由25名年龄匹配的健康个体组成，他们将接受与MCI组相同的测试。一只带有铁调节蛋白2“敲除”的基因工程小鼠将被用来验证我们的新技术。这种基因敲除会积累异常数量的脑铁，并表现出神经退行性疾病。IRP-2基因的多态搜索将是每个患者评估的一部分。在四年的连续随访中，预计75名研究对象中约有15%将患有阿尔茨海默病，并将利用统计咨询和尸检信息建立心理测量数据、脑铁定位和定量以及免疫细胞化学外周血液之间的相关性。