Proteomics of Hypertension and Alzheimer's Disease in African Americans

非裔美国人高血压和阿尔茨海默病的蛋白质组学

• 批准号: 10629345
• 负责人: Rena A. S. Robinson
• 金额: $ 79.72万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629345
• 关键词: Adult; Affect; African American; African American population; Age; Age Years; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Amyloid deposition; Antihypertensive Agents; Architecture; Area; Autopsy; Biochemical Markers; Biochemical Pathway; Biological; Biological Assay; Biology; Blood; Brain; Cerebral small vessel disease; Chemosensitization; Cholesterol Homeostasis; Clinical; Cognition; Collaborations; Data; Development; Diabetes Mellitus; Diagnosis; Disease; Disparity; Elderly; Goals; High Prevalence; Hypertension; Immune response; Impaired cognition; Incidence; Laboratories; Link; Lipids; Literature; MAP4; Measures; Mediator; Memory; Molecular; Molecular Profiling; Not Hispanic or Latino; Participant; Pathogenesis; Pathologic; Pathway interactions; Pharmaceutical Preparations; Physiological; Planet Mars; Plasma; Play; Population; Prevalence; Proteins; Proteomics; Pulse Pressure; Race; Role; Sampling; Signal Transduction; Synapses; Testing; University resources; Vascular Diseases; Woman; brain tissue; cardiovascular risk factor; caucasian American; clinical center; cohort; differential expression; diverse data; fatty acid transport; functional disability; high risk; hypercholesterolemia; hypertensive; innovation; lipid metabolism; men; middle age; mitochondrial dysfunction; mortality; neuropathology; normotensive; offspring; protein biomarkers; proteomic signature; racial disparity; repository; response; vascular risk factor

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.

项目概要 非裔美国人 (AA) 患阿尔茨海默病 (AD) 及相关疾病的可能性是其他人的两到三倍 迄今为止，AD 患者中 20% 的人患有痴呆症，而只有非西班牙裔白人 (NHW) 患有痴呆症。 占美国 AD 人口 13% 的人也有较高的血管危险因素发生率。 包括高血压、高胆固醇血症和糖尿病 AA 在美国的高血压患病率。 47% 发生在成年早期，高血压是 AD 和相关痴呆症的主要危险因素。 由于高血压和 AD 之间的这种内在关系，特别是在 AA 中， 必须提出这样一个问题：“将高血压和 AD 联系起来的潜在生化途径是什么？ 该提案通过“审查差异的调解者”直接回应了 PA-15-349 的目标。 阿尔茨海默病，特别是使用不同的受试者群体来检查生化标志物”。 初步结果显示，高血压是种族差异的一个中介因素，会增加 AA 的 AD 风险。 我们实验室获得的蛋白质组学数据，我们的工作假设是免疫中共享的生物反应 反应和脂质代谢途径导致 AA 地区高血压和 AD 的高患病率。 免疫反应和脂质代谢途径的改变被公认为是 AD 的促成因素， 我们在该领域组建了一支由跨学科专家组成的一流团队。 阿尔茨海默氏症和血管疾病，并将研究来自不同非洲裔美国人群体的生物样本 关注高血压、AD 或 AD 风险的参与者：BioVU、Rush ADC Clinical Core/MARS/ROSMAP、 范德比尔特 MAP 和后代我们将使用先进的蛋白质组学方法来研究血浆和尸检。 来自这些队列参与者的脑组织并完成两个主要目标 1. 建立 AA 中高血压的分子特征和目标 2. 建立 AD 中的分子特征 成功鉴定蛋白质组学特征将有助于更好地了解 AD 发病机制和 高血压的分子结构是 AA 中 AD 的主要血管危险因素。 创新、雄心勃勃、极其紧迫，并将提供有关人群疾病生物学的关键信息 在当前的文献中，这种情况的代表性不足。