Core F: Biomarker Core

核心 F：生物标志物核心

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos 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

项目摘要

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记核心为堪萨斯大学阿尔茨海默病进行液体生物标记评估疾病研究中心（KU ADRC）。对于队列参与者，我们确定淀粉样蛋白-tau-神经变性脑脊液 (CSF) 和血浆中的 (ATN) 水平；测量血浆炎症、神经营养素和代谢相关终点；并获得血液和大脑线粒体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基础线粒体基因组学和代谢的创新和独特资源（米高梅）核心。 MGM Core 开发了新型线粒体和代谢生物标志物，并使用了这些生物标志物生物标志物作为临床试验目标参与终点。它还确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 MGM Core 还提供了最先进的为研究人员提供咨询和技术支持，生物标记核心提供这些服务。细胞通过 MGM Core 提供的模型包括细胞质杂种 (cybrid) 细胞系、诱导多能细胞系干细胞 (iPSC) 系、由 iPSC 分化的神经元和神经胶质细胞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，并培育了新兴的 ADRD 领域对 ATN 生物标志物与 mtDNA 特征、线粒体功能和能量代谢的关联感兴趣。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、我们为国内和国际用户提供非常有价值的代谢导向服务、专业知识和试剂在我们的前两个周期中提供。它保持了我们在了解 AD 成因方面的领先地位线粒体和能量代谢功能障碍、该功能障碍的后果以及如何出于治疗或预防目的操纵线粒体和能量代谢。在此周期内 Biomarker Core 将通过重点关注以下具体目标来实现其目标：(1) 执行液体和组织生物标志物评估； (2) 追求线粒体和代谢生物标志物的开发；和（3）提供细胞模型、技术服务和新型生物标志物。