NEUROANATOMICAL BIOMARKERS OF EARLY AD

AD 早期的神经解剖学生物标志物

• 批准号: 6989343
• 负责人: JOHN G CSERNANSKY
• 金额: $ 13.98万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989343
• 关键词: Alzheimer' s disease; apolipoprotein E; bioimaging /biomedical imaging; biomarker; brain morphology; cerebrospinal fluid; cingulate gyrus; clinical research; cognition; computational neuroscience; disease /disorder proneness /risk; entorhinal cortex; hippocampus; human middle age (35-64); human old age (65+); human subject; magnetic resonance imaging; neurochemistry; neuropathology

Alzheimer's disease (AD) is the most common dementing illness of late life, and robs persons of vigorous activity and productivity in their later years. Future drug treatments may be capable of slowing the progression of the disease or even preventing its clinical appearance, and when such treatments become available, the ability to detect the illness in its earliest stages will be needed to take full advantage of them. The overall goal of this project is to test the use of structural magnetic resonance scanning and the tools of computational anatomy to distinguish nondemented subjects at elevated risk for developing dementia of the Alzheimer type (DAT) from age- and gender-matched comparison subjects. The primary strategy for identifying subjects at elevated risk for developing DAT will be having a parent with DAT; allelic status for the apolipoprotein E gene will be a secondary strategy. High resolution magnetic resonance (MR) scans will be collected from all subjects at entry into the study, and for subjects who are recruited during the first two years of the Project, repeat MR scans will be collected after three years. The specific aims of the project include a comparison of the structural characteristics of the hippocampus, parahippocampal gyrus (including the entorhinal cortex) and cingulate gyrus (anterior and posterior segments) in nondemented subjects with (N = 120) and without (n = 120) a parent with DAT. The total group of subjects will then be resorted according to the number of E4 alleles for apolipoprotein E, and a comparison of subjects with or without one or more E4 alleles will be made. If there are neuroanatomical differences in the groups of subjects with and without one or more E4 alleles, then the impact of the apoE4 allele on the effect of having a parent with DAT will be investigated. In addition, we will determine whether there are correlations between neuroanatomical measures that discriminate between subjects at elevated risk for developing DAT and comparison subjects and other predictive variables assessed by other Projects.

阿尔茨海默氏病（AD）是后期生活中最常见的痴呆疾病，在后来的几年中，抢劫了剧烈的活动和生产力。未来的药物治疗可能能够减缓疾病的进展，甚至可以防止其临床外观，并且当这种治疗可用时，需要在最早的阶段检测疾病的能力，以充分利用它们。该项目的总体目的是测试结构磁共振扫描的使用以及计算解剖学的工具，以区分患阿尔茨海默氏症类型（DAT）痴呆症风险较高的非训练受试者与年龄和性别匹配的比较受试者。识别患有较高风险的受试者DAT的主要策略是患有DAT的父母。载脂蛋白E基因的等位基因状态将是次要策略。高分辨率的磁共振（MR）扫描将从进入研究时的所有受试者中收集，对于在项目的前两年中招募的受试者，将在三年后收集重复MR扫描。该项目的具体目的包括比较海马的结构特征，parahampocampal回和在非（n = 120）和（n = 120）的dat的父母中，在非对受试者中的扣带回回（前部和后段）和扣带回的回去（前部和后段）。然后，将根据载脂蛋白E的E4等位基因的数量来求解一组受试者，并比较有或没有一个或多个E4等位基因的受试者。如果有或没有一个或多个E4等位基因的受试者组存在神经解剖学差异，则APOE4等位基因对具有的影响 将调查患有DAT的父母。此外，我们还将确定神经解剖学措施之间是否存在相关性，这些措施区分了较高的DAT和比较主题风险的受试者以及其他项目评估的其他预测变量。