Proteomics of Hypertension and Alzheimer's Disease in African Americans

项目摘要 非裔美国人（AAs）患阿尔茨海默病（AD）和相关疾病的可能性是其他人的两到三倍。 非西班牙裔白人（NHWs）到目前为止，AA占AD患者的20%，而只有 占美国人口的13%。患有AD的AA也具有较高的血管风险因素发生率 包括高血压、高胆固醇血症和糖尿病。美国AA的高血压患病率 是47%，发生在成年早期。高血压是AD和相关痴呆的主要危险因素， 在中年的时候，由于高血压和AD之间的这种内在关系，特别是在AA中， 必须提出的问题是：“高血压和AD之间的潜在生化途径是什么？ “AA”？这项建议直接响应PA-15-349的目标，“审查 阿尔茨海默病，使用不同的受试者队列”。特别地，我们建议检查生化标志物， 高血压，这是种族差异的中介，并增加了AA中的AD风险。根据初步 在我们实验室获得的蛋白质组学数据中，我们的工作假设是免疫系统中的共同生物反应， 反应和脂质代谢途径导致AA中高血压和AD的高发。 免疫反应和脂质代谢途径的改变被公认为AD的促成因素， 也在高血压中发挥作用。我们已经组建了一个跨学科专家的一流团队， 阿尔茨海默氏症和血管疾病，并将研究来自不同群体的非裔美国人的生物标本， 关注高血压、AD或AD风险的参与者：BioVU、Rush ADC临床核心/MARS/ROSMAP， 范德比尔特地图和后代。我们将使用先进的蛋白质组学方法来研究血浆和死后 从这些队列中的参与者的脑组织，并完成两个主要目标。目标1.建立 AAs和Aim 2中高血压的分子特征。建立AD的分子特征， 原子吸收法成功识别蛋白质组学特征将有助于更好地了解AD发病机制， 高血压的分子结构，这是AA中AD的主要血管危险因素。这一建议高度 创新，雄心勃勃，非常紧迫，并将提供有关人口疾病生物学的关键信息， 这在当前的文献中被低估了。

Project Summary African Americans (AAs) are two to three times more likely to have Alzheimer's disease (AD) and related- dementias than Non-Hispanic Whites (NHWs). AAs comprise 20 percent of AD sufferers to-date, while only making up 13 percent of the US population. AAs with AD also have high incidences of vascular risk factors including hypertension, hypercholesterolemia, and diabetes. The prevalence of hypertension for AAs in the US is 47% and occurs at early adult ages. Hypertension is a major risk factor for AD and related-dementias especially when present in mid-life. Because of this inherent relationship between hypertension and AD especially in AAs, the question must be asked “What are the underlying biochemical pathways that link hypertension and AD in AAs”? This proposal directly responds to the goal of PA-15-349 by “examining mediators of disparities in Alzheimer's disease, using diverse cohorts of subjects”. Specially, we propose to examine biochemical markers of hypertension, which is a mediator of racial disparities and increases AD risk in AAs. Based on preliminary proteomics data in obtained our laboratory, our working hypothesis is that shared biological responses in immune response and lipid metabolism pathways contribute to both high prevalence of hypertension and AD in AAs. Alterations in both immune response and lipid metabolism pathways are well recognized as contributors to AD, and also play roles in hypertension. We have assembled a stellar team of interdisciplinary experts in the areas of Alzheimer's and vascular diseases and will study biospecimens from diverse cohorts of African American participants that focus on hypertension, AD, or AD risk: BioVU, Rush ADC Clinical Core/MARS/ROSMAP, Vanderbilt MAP, and Offspring. We will use advanced proteomic approaches to study plasma and postmortem brain tissue from participants in these cohorts and complete two primary aims. Aim 1. Establishing the molecular signature of hypertension in AAs and Aim 2. Establishing the molecular signature of AD in AAs. Successfully identifying proteomics signatures will lead to a better understanding of AD pathogenesis and the molecular architecture of hypertension, a major vascular risk factor for AD in AAs. This proposal is highly innovative, ambitious, extremely urgent, and will provide critical information about disease biology in a population that has been underrepresented throughout the current literature.