Integrative analysis of multi-omics data to delineate CCL2 associated inflammatory pathways in Alzheimers Disease

多组学数据综合分析以描绘阿尔茨海默病中 CCL2 相关炎症通路

基本信息

  • 批准号:
    10369676
  • 负责人:
  • 金额:
    $ 16.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-03-15 至 2024-02-29
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) is the most common cause of dementia worldwide. In the US, it is the fifth leading cause of death in people over 65 years of age. Delineating factors that predict rate of future cognitive decline and dementia are important but are yet to be thoroughly understood. Knowledge of disease progression related biological factors will be critical in designing novel therapeutic strategies to mitigate their deleterious effects and thereby prevent the associated cognitive and behavioral decline. The research at the foundation of this R03 is a clinical translational study that uses systems biology and bioinformatics techniques to characterize the genetic and cellular context of dysregulated inflammatory pathways in the brain and periphery that impact longitudinal cognitive decline in different stage of Alzheimer's disease. Our earlier work among clinical patients at the Mild cognitive impairment stage AD suggests that a clinically meaningful degree of rapid cognitive decline was best predicted by baseline levels of an inflammatory analyte CCL2. In this work we hope to extend this initial insight by characterizing in depth the genetic drivers behind the inflammatory deregulation in clinical AD and the cellular context in which it occurs in the periphery and the central nervous system. We will confirm and validate these changes with genome wide (RNA-seq) expression changes and against data from other large national data (ADNI, Accelerating Medicines Partnership-AD) and by single cell transcriptomics of immune cells in the cerebrospinal fluid among well characterized patients. If the hypothesis and models are validated, scientific insights from this research will help identify novel therapeutic targets and individual propensities for deleterious inflammatory responses for future precision medicine interventions against neuroinflammation in AD to prevent disease progression and cognitive decline. If the hypothesis is found to be not true, the findings from this study will still represent a significant advance in our knowledge of variability in individual propensities to have a neuroinflammatory response in the face of neurodegenerative disease pathology. The results of this will be useful both clinically and in designing and interpreting future research outcomes.
项目总结/摘要 阿尔茨海默病(AD)是全球痴呆症最常见的原因。在美国,它是第五大 是65岁以上人群的死亡原因。描述预测未来认知能力下降率的因素 和痴呆症是重要的,但尚未被彻底理解。疾病进展相关知识 生物学因素在设计新的治疗策略以减轻其有害作用方面将是至关重要的, 从而防止相关的认知和行为衰退。 R 03的基础研究是一项临床转化研究,使用系统生物学, 生物信息学技术来表征失调的炎症通路的遗传和细胞背景 影响阿尔茨海默病不同阶段的纵向认知能力下降。我们 早期在轻度认知障碍阶段AD的临床患者中的研究表明, 炎症分析物的基线水平最能预测有意义程度的快速认知能力下降 CCL2。在这项工作中,我们希望通过深入描述基因驱动因素, 临床AD中的炎性失调及其在外周和中枢发生的细胞环境 神经系统我们将通过全基因组(RNA-seq)表达变化来确认和验证这些变化 并与其他大型国家数据(ADNI,加速药物合作伙伴关系-AD)的数据进行对比, 在充分表征的患者中,脑脊液中免疫细胞的细胞转录组学。如果假设 和模型得到验证,这项研究的科学见解将有助于确定新的治疗靶点, 有害炎症反应的个体倾向,用于未来的精确医学干预, AD中的神经炎症,以防止疾病进展和认知能力下降。如果假设被发现是 虽然这不是真的,但这项研究的结果仍然代表了我们对变异性的认识的重大进步。 在面对神经退行性疾病时具有神经炎症反应的个体倾向 病理这一结果将是有用的临床和设计和解释未来的研究 结果。

项目成果

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Gurkan Bebek其他文献

Gurkan Bebek的其他文献

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{{ truncateString('Gurkan Bebek', 18)}}的其他基金

Integrative analysis of proteomics and transcriptomics to delineate vesicular transport related protein abnormalities related to Alzheimer's, Lewy body and mixed Pathologies
蛋白质组学和转录组学的综合分析,以描述与阿尔茨海默病、路易体和混合病理学相关的囊泡运输相关蛋白质异常
  • 批准号:
    10444050
  • 财政年份:
    2022
  • 资助金额:
    $ 16.1万
  • 项目类别:
Developing a clinical and research framework for evaluating inflammation pathway dysregulation in Alzheimer's disease
开发评估阿尔茨海默病炎症途径失调的临床和研究框架
  • 批准号:
    10323668
  • 财政年份:
    2021
  • 资助金额:
    $ 16.1万
  • 项目类别:

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