Iron Metabolism Alterations in Alzheimer's Disease

描述（由申请人提供）：指导这项生物工程研究合作的机构是洛马琳达大学（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BioErgonomics， Inc., St Paul， MN和MRI Institute for Biomedical Research， St. Louis， MO。我们的多学科生物工程研究伙伴关系的目标是在老年MCI患者的背景下，确定改变的脑铁代谢作为阿尔茨海默病的危险因素的作用。该研究的工程重点是：(1)定义外周血细胞中表明铁或淀粉样蛋白扰动的离体标志物；(2)开发一种新的磁共振成像（MRI）技术来定量和区分脑铁。研究对象为75例（50岁或以上）轻度认知障碍患者，他们将被纵向随访3 - 4年，包括连续的心理测试、特殊的MRI序列和外周血细胞研究。对照受试者将由25名年龄匹配的健康个体组成，他们将接受与轻度认知障碍组相同的测试。一只铁调节蛋白2“敲除”的基因工程小鼠会积累异常数量的脑铁，并表现出神经退行性疾病，将用于验证我们的新技术。寻找IRP-2基因的多态性将是每位患者评估的一部分。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，心理测量数据、脑铁定位和定量以及免疫细胞化学外周血的相关性将通过统计咨询和尸检信息建立。

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.