MIRAGE STAR

海市蜃楼之星

• 批准号: 7720616
• 负责人: Elizabeth O. Ofili
• 金额: $ 9.76万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720616
• 关键词: Acceleration; African American; Age; Alzheimer' s Disease; Apolipoprotein E; Attention; Blood Pressure; Blood Vessels; Blood specimen; Brain; Brain imaging; Canada; Caucasians; Caucasoid Race; Child; Cognitive; Computer Retrieval of Information on Scientific Projects Database; DNA; Data; Disease; Enrollment; Epidemiologic Studies; Ethnic group; Family; Family-Based Registry; First Degree Relative; Funding; Genes; Genetic; Genotype; Germany; Grant; Health; Image; Injury; Institution; Japanese American; Life; Magnetic Resonance Imaging; Mediating; Medical History; Methodology; Mirage; Nerve Degeneration; Numbers; Outcome; Participant; Patients; Phase; Plasma; Population; Predisposition; Process; Protein Isoforms; Protocols documentation; Questionnaires; Recording of previous events; Recruitment Activity; Relative (related person); Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Screening procedure; Siblings; Single Nucleotide Polymorphism; Source; Spouses; Testing; United States National Institutes of Health; Vascular Diseases; Work; base; cerebrovascular; genotyping technology; hypertension treatment; instrument; neuroimaging; proband

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. Our attention is turned to the growing body of evidence from pathological, epidemiological and genetic studies that state that risk factors for vascular disease also enhance risk of AD in this study. However, since most epidemiological studies lack neuroimaging data, it is unclear whether the apparent association between vascular risk factors and AD is mediated via ischemic injury to the brain, acceleration of the primary Alzheimer neurodegenerative process, or some other process. Some vascular risk factors are more prevalent in African American and Japanese American populations than in Caucasians. We propose to build upon our earlier work by evaluating the association between APOE, genes involved in vascular function, and other indicators of cerebrovascular health, including blood pressure and structural brain imaging (MR1), and susceptibility to AD in these ethnic groups. In order to carry out this project successfully, we will ascertain a sample of 1000 patients (500 Caucasian, 300 African American, 200 Japanese American) who meet NINCDS/ADRDA criteria for probable or definite AD from 11 centers in the U.S., Canada and Germany. Many patients will be identified from our existing family registry. Family history, medical history, and epidemiological information will be obtained from AD probands and their first-degree relatives using standardized questionnaire instruments and established protocols. A cognitive screening test will be administered to and blood samples will be collected from the proband 's living sibs, spouses and children over the age of 50 years. DNA, plasma Ap isoforms and MRI of the brain will be evaluated in probands and sibs. The scientific aims of this project are: 1. To examine recently discovered associations between risk of AD and magnetic resonance imaging (MRl) variables, adjusting for APOE genotype and other known risk factors. 2. To examine the association between single nucleotide polymorphisms (SNPs) in lOO genes posited to have a role in vascular function and AD in 1000 siblings using high throughput genotyping technology, and sib-pair linkage and family-based association methodologies. 3. To compare the relative contributions of these SNPs and other factors, including blood pressure, treatment for hypertension, and plasma A on disease and imaging outcomes in Caucasian, African American and Japanese American siblings. The targeted enrollment numbers include 100 probands and at least one sibling. Progress 2003-2004 This study is still in the recruitment phase. Twenty-five probands and with at least one sibling will be recruited per year for four years. Twenty-three families have been recruited this year with 15 cases completed, inclusive of 60 participants. Thirty MRIs and 15 cases have been completed.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们的注意力转向来自病理学、流行病学和遗传学研究的越来越多的证据，这些证据表明，在本研究中，血管疾病的危险因素也会增加 AD 的风险。然而，由于大多数流行病学研究缺乏神经影像学数据，目前尚不清楚血管危险因素与 AD 之间的明显关联是否是通过大脑缺血性损伤、原发性阿尔茨海默氏症神经退行性过程加速或其他过程介导的。一些血管危险因素在非裔美国人和日裔美国人中比白种人更普遍。我们建议在我们早期工作的基础上，评估 APOE、涉及血管功能的基因和其他脑血管健康指标（包括血压和结构性脑成像 (MR1)）以及这些种族群体对 AD 的易感性之间的关联。为了成功开展该项目，我们将从美国、加拿大和德国的 11 个中心确定符合 NINCDS/ADRDA 可能或明确 AD 标准的 1000 名患者样本（500 名白种人、300 名非裔美国人、200 名日裔美国人）。许多患者将从我们现有的家庭登记中被识别出来。家族史、病史和流行病学信息将使用标准化问卷工具和既定方案从 AD 先证者及其一级亲属获得。将对先证者的在世同胞、配偶和 50 岁以上的子女进行认知筛查测试，并采集血液样本。将在先证者和同胞中评估大脑的 DNA、血浆 Ap 亚型和 MRI。该项目的科学目标是： 1.检查最近发现的AD风险和磁共振成像(MR1)变量之间的关联，调整APOE基因型和其他已知的风险因素。 2.使用高通量基因分型技术以及同胞对连锁和基于家族的关联方法，检查被认为对1000名兄弟姐妹的血管功能和AD起作用的100个基因中的单核苷酸多态性(SNP)之间的关联。 3. 比较这些 SNP 和其他因素（包括血压、高血压治疗和血浆 A）对白种人、非裔美国人和日裔美国人兄弟姐妹的疾病和影像学结果的相对贡献。 目标注册人数包括 100 名先证者和至少一名兄弟姐妹。 2003-2004 年进展 这项研究仍处于招募阶段。 四年内，每年将招募 25 名先证者和至少一名兄弟姐妹。今年共招募了23个家庭，完成了15个案例，包括60名参与者。已完成 30 例 MRI 和 15 例病例。