Proteomics of Hypertension and Alzheimer's Disease in African Americans

项目摘要 非裔美国人(AA)患阿尔茨海默病(AD)和相关疾病的可能性是美国人的两到三倍 痴呆症患者比非西班牙裔白人(NHW)多。到目前为止，AAS占AD患者的20%，而只有 占美国人口的13%。AAS合并AD的血管危险因素的发生率也很高 包括高血压、高胆固醇血症和糖尿病。美国腹主动脉系统的高血压患病率 是47%，发生在成年早期。高血压是阿尔茨海默病的主要危险因素，尤其是与痴呆相关的 当出现在中年的时候。由于高血压和AD之间的这种内在关系，特别是在AA中， 这个问题必须被问到：在高血压和AD之间有什么潜在的生化途径？ AAS“？该提案直接回应了PA-15-349的目标，即检查不一致的调解人 阿尔茨海默病，使用不同的受试者队列“。特别是，我们建议检测生化标记物 高血压是种族差异的调节因素，并增加了再障患者患AD的风险。基于初步的 在我们实验室获得的蛋白质组学数据中，我们的工作假设是共同的生物反应在免疫 反应和脂代谢途径导致了AAS高血压和AD的高患病率。 免疫反应和脂质代谢途径的改变都被认为是AD的贡献者， 在高血压中也扮演着重要角色。我们已经在这些领域组建了一支由跨学科专家组成的优秀团队 阿尔茨海默氏症和血管疾病的研究，并将研究来自不同非裔美国人队列的生物标本 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身体 来自这些队列参与者的脑组织，并完成两个主要目标。目标1.建立 AAS中高血压的分子标记和目的2.建立AD的分子标记 美国医学会。成功识别蛋白质组学特征将有助于更好地理解AD的发病机制和 高血压的分子结构，这是AAS中AD的主要血管危险因素。这项提议是非常重要的 创新、雄心勃勃、极其紧迫，并将提供关于人群中疾病生物学的关键信息 在目前的文学中，这一点一直没有得到充分的体现。

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.