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; 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.

项目摘要 非裔美国人（AAS）患阿尔茨海默氏病（AD）和相关 - 痴呆症比非西班牙裔白人（NHW）。 AAS占迄今为止的20％的广告患者，而仅限 占美国人口的13％。 AAS具有广告的AA还具有很高的血管危险因素 包括高血压，高胆固醇血症和糖尿病。 AAS在美国的高血压患病率 为47％，发生在成年早期。高血压是AD和相关止动物的主要危险因素 当出现在中年时。由于高血压与AD之间的这种固有关系，尤其是在AAS中 必须问：“将高血压和广告联系起来的基础生化途径是什么 AAS”？该提案直接响应PA-15-349的目标 阿尔茨海默氏病，使用潜水员同类的学科”。特别是，我们建议检查生化标志物 高血压是种族分布的中介，并增加了AAS的AD风险。基于初步 蛋白质组学数据在获得我们的实验室中，我们的工作假设是免疫中共享的生物学反应 反应和脂质代谢途径在AAS中有助于高血压的高流行率。 免疫响应和脂质代谢途径的改变都被公认为是AD的贡献者， 并在高血压中发挥作用。我们已经组建了一支由跨学科专家组成的出色团队 阿尔茨海默氏症和血管疾病，并将研究非裔美国人潜水队同类的生物测量 专注于高血压，AD或AD风险的参与者：BIOVU，RUSH ADC临床核心/火星/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验尸 来自这些队列的参与者的脑组织，并完成两个主要目标。目标1。建立 AAS中高血压的分子特征和目标2。建立AD的分子特征 AAS。成功识别蛋白质组学特征将导致对AD发病机理和 高血压的分子结构，这是AAS中AD的主要血管危险因素。该提议很高 创新，雄心勃勃，极为紧急，并将提供有关人群中疾病生物学的关键信息 在当前文献中，这已经不足了。