Core F: Biomarker Core

核心 F：生物标志物核心

• 批准号: 10264628
• 负责人: RUSSELL H. SWERDLOW
• 金额: $ 57.1万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264628
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Biological Assay; Biological Markers; Blood; Brain; Brain-Derived Neurotrophic Factor; CCL2 gene; Cell Line; Cell model; Cells; Cerebrospinal Fluid; Clinical; Clinical Trials; Combination Drug Therapy; Consultations; DNA Sequence; DNA sequencing; Data Set; Disease; Energy Metabolism; Eotaxin; Foundations; Functional disorder; Funding; Genomics; Goals; Hybrids; Inflammation; Insulin; International; Kansas; Liquid substance; Measures; Metabolism; Mitochondria; Mitochondrial DNA; Nerve Degeneration; Neuroglia; Neurons; Participant; Plasma; Prevention; Prevention strategy; Prognostic Marker; Reagent; Research; Research Personnel; Research Project Grants; Resources; Services; TNF gene; Therapeutic; United States National Institutes of Health; Universities; Vascular Endothelial Growth Factors; base; biomarker development; cohort; diagnostic biomarker; drug development; drug repurposing; effective therapy; induced pluripotent stem cell; innovation; interest; lymphoblast; meetings; mitochondrial metabolism; neurotrophic factor; novel; novel marker; prevent; programs; tau Proteins; therapy development; tissue biomarkers; tool; treatment strategy; working group

ABSTRACT: BIOMARKER CORE The Biomarker Core performs fluid biomarker assessments for the University of Kansas Alzheimer's Disease Research Center (KU ADRC). For Cohort participants we determine amyloid-tau-neurodegeneration (ATN) levels in cerebrospinal fluid (CSF) and plasma; measure plasma inflammation, neurotrophin, and metabolism-relevant endpoints; and obtain blood and brain mitochondrial DNA (mtDNA) sequences. In addition to meeting the Center's need for standard ATN biomarker assessments, the Biomarker Core maintains the innovation and unique resources of our foundational Mitochondrial Genomics and Metabolism (MGM) Core. The MGM Core developed novel mitochondrial and metabolism biomarkers and used those biomarkers as clinical trial target engagement endpoints. It also identified mitochondria and metabolism- associated diagnostic and prognostic biomarkers. The original MGM Core also offered state-of-the-art consultation and technical support to investigators and here the Biomarker Core delivers these services. Cell models available through the MGM Core including cytoplasmic hybrid (cybrid) cell lines, induced pluripotent stem cell (iPSC) lines, neurons and glia differentiated from iPSCs, and lymphoblast cell lines remain available through the Biomarker Core. Adding ATN assessments enriches our Clinical Cohort dataset and nurtures an emerging ADRD field-wide interest in correlating ATN biomarkers with mtDNA signatures, mitochondrial function, and energy metabolism. Extending these services to investigators benefits their research projects and programs. It provides our local, national, and international users the much-valued metabolism-oriented service, expertise and reagents we provided during our previous two cycles. It maintains our preeminence in understanding the causes of AD mitochondrial and energy metabolism dysfunction, the consequences of that dysfunction, and how to manipulate mitochondria and energy metabolism with therapeutic or prevention intent. During this cycle the Biomarker Core will accomplish its goals by focusing on the following Specific Aims: (1) Perform fluid and tissue biomarker assessments; (2) Pursue mitochondrial and metabolism biomarker development; and (3) Provide cell models, technical services, and novel biomarkers.

摘要：生物标志物核心 生物标志物核心为堪萨斯大学阿尔茨海默氏症进行流体生物标志物评估 疾病研究中心（KU ADRC）。对于队列参与者，我们确定淀粉样蛋白-tau-神经变性 (ATN)脑脊液（CSF）和血浆中的水平;测量血浆炎症、神经营养因子和 代谢相关终点;并获得血液和脑线粒体DNA（mtDNA）序列。 除了满足中心对标准ATN生物标志物评估的需求外，生物标志物核心 保持我们的基础线粒体基因组学和代谢的创新和独特资源 (MGM)核心米高梅核心开发了新的线粒体和代谢生物标志物，并使用这些 生物标志物作为临床试验目标参与终点。它还鉴定了线粒体和新陈代谢- 相关的诊断和预后生物标志物。最初的米高梅核心还提供了最先进的 为研究者提供咨询和技术支持，在这里，生物标志物核心提供这些服务。细胞 通过MGM核心可获得的模型包括细胞质杂交（cybrid）细胞系、诱导多能 干细胞（iPSC）系、从iPSC分化的神经元和神经胶质以及淋巴母细胞系仍然可用 通过生物标记核心 添加ATN评估丰富了我们的临床队列数据集，并培养了新兴的ADRD领域 ATN生物标志物与线粒体DNA特征、线粒体功能和能量代谢的相关性。 将这些服务扩展到研究人员，有利于他们的研究项目和计划。它提供了我们当地的， 国内和国际用户非常重视代谢导向的服务，专业知识和试剂，我们 在前两个周期中，它保持了我们在了解AD原因方面的优势 线粒体和能量代谢功能障碍，这种功能障碍的后果，以及如何 以治疗或预防为目的操纵线粒体和能量代谢。在这个周期中， 生物标志物核心将通过专注于以下具体目标来实现其目标：（1）执行流体和 组织生物标志物评估;（2）进行线粒体和代谢生物标志物开发;以及（3） 提供细胞模型、技术服务和新型生物标志物。