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
基本信息
- 批准号:10629345
- 负责人:
- 金额:$ 79.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AdultAffectAfrican AmericanAfrican American populationAgeAge YearsAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease related dementiaAlzheimer&aposs disease riskAmyloid depositionAntihypertensive AgentsArchitectureAreaAutopsyBiochemical MarkersBiochemical PathwayBiologicalBiological AssayBiologyBloodBrainCerebral small vessel diseaseChemosensitizationCholesterol HomeostasisClinicalCognitionCollaborationsDataDevelopmentDiabetes MellitusDiagnosisDiseaseDisparityElderlyGoalsHigh PrevalenceHypertensionImmune responseImpaired cognitionIncidenceLaboratoriesLinkLipidsLiteratureMAP4MeasuresMediatorMemoryMolecularMolecular ProfilingNot Hispanic or LatinoParticipantPathogenesisPathologicPathway interactionsPharmaceutical PreparationsPhysiologicalPlanet MarsPlasmaPlayPopulationPrevalenceProteinsProteomicsPulse PressureRaceRoleSamplingSignal TransductionSynapsesTestingUniversity resourcesVascular DiseasesWomanbrain tissuecardiovascular risk factorcaucasian Americanclinical centercohortdifferential expressiondiverse datafatty acid transportfunctional disabilityhigh riskhypercholesterolemiahypertensiveinnovationlipid metabolismmenmiddle agemitochondrial dysfunctionmortalityneuropathologynormotensiveoffspringprotein biomarkersproteomic signatureracial disparityrepositoryresponsevascular risk factor
项目摘要
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)迄今为止,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。
免疫应答和脂质代谢途径的改变被公认为AD的贡献者,
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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rena A. S. Robinson的其他文献
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{{ truncateString('Rena A. S. Robinson', 18)}}的其他基金
Elucidating Molecular Drivers of Aging and Alzheimer's Disease via Multimodal Imaging Mass Spectrometry
通过多模态成像质谱阐明衰老和阿尔茨海默病的分子驱动因素
- 批准号:
10516633 - 财政年份:2022
- 资助金额:
$ 79.72万 - 项目类别:
Ensuring success in academia for underrepresented faculty to advance biomedical science research
确保代表性不足的教师在学术界取得成功,以推进生物医学科学研究
- 批准号:
10509091 - 财政年份:2022
- 资助金额:
$ 79.72万 - 项目类别:
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:
10002175 - 财政年份:2019
- 资助金额:
$ 79.72万 - 项目类别:
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:
10412968 - 财政年份:2019
- 资助金额:
$ 79.72万 - 项目类别:
Novel multiplexing proteomics to study the periphery in Alzheimer's disease
研究阿尔茨海默病外围的新型多重蛋白质组学
- 批准号:
9521234 - 财政年份:2016
- 资助金额:
$ 79.72万 - 项目类别:
Novel Multiplexing Proteomics to Study the Periphery in Alzheimer's Disease
研究阿尔茨海默氏病外围的新型多重蛋白质组学
- 批准号:
9011321 - 财政年份:2016
- 资助金额:
$ 79.72万 - 项目类别:
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