MIRAGE STAR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在这项研究中，我们的注意力转向越来越多的来自病理学、流行病学和遗传学研究的证据，这些证据表明，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数据，尚不清楚血管危险因素与AD之间的明显联系是通过脑缺血损伤、加速原发阿尔茨海默氏神经退变过程或其他过程介导的。一些血管危险因素在非裔美国人和日裔美国人中比在高加索人中更普遍。我们建议通过评估载脂蛋白E、参与血管功能的基因和包括血压和结构性脑成像(MR1)在内的其他脑血管健康指标与这些民族中AD易感性之间的关联，来建立我们早期的工作。为了成功实施这一项目，我们将从美国、加拿大和德国的11个中心确定符合NINCDS/ADRDA标准的1000名患者样本(500名高加索人，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识别出来。家族史、病史和流行病学信息将使用标准化的问卷工具和既定的方案从AD先证者及其一级亲属那里获得。将对先证者S的在世同胞、配偶和50岁以上的子女进行认知筛查测试，并采集血样。先证者和同胞的脱氧核糖核酸、血浆AP亚型和核磁共振成像将进行评估。该项目的科学目标是： 1.研究最近发现的AD风险与磁共振成像(MRL)变量之间的关联，调整APOE基因和其他已知风险因素。 2.采用高通量基因分型技术、同胞对连锁和家系关联方法，研究1000名同胞中与血管功能有关的LOO基因的单核苷酸多态(SNPs)与AD的相关性。 3.比较这些SNPs与其他因素(包括血压、高血压治疗和血浆A)在高加索人、非裔美国人和日裔美国人兄弟姐妹中对疾病和影像结果的相对贡献。 目标注册人数包括100名先证者和至少一名兄弟姐妹。 进度2003-2004 这项研究仍处于招募阶段。每年将招募25名至少有一名兄弟姐妹的先知，为期四年。今年招募了23个家庭，完成了15个案例，包括60个参与者。已经完成了30次核磁共振检查和15例病例。

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.