Biomarker Core

生物标志物核心

基本信息

批准号：
10655669
负责人：
Berislav V Zlokovic
金额：
$ 31.81万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10655669
关键词：
Aliquot Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer’s disease biomarker Amyloid beta-Protein Astrocytes Biological Assay Biological Markers Blood Blood - brain barrier anatomy Blood Vessels Brain Cells Centrifugation Cerebrospinal Fluid Cerebrovascular system Clinical Cognitive Cohort Studies Collaborations Collection Consent Custom Cyclophilin A Data Data Analyses Dementia Deposition Detection Endothelial Cells Ensure Enzyme-Linked Immunosorbent Assay Ferritin Functional disorder Genotype Goals Grant Growth Factor Guidelines Human Image Impaired cognition Inflammatory Response Information Systems Injury Knowledge Leadership Measurement Metabolic Microglia Neuronal Injury Neurons Participant Pathogenesis Pericytes Peripheral Blood Mononuclear Cell Pilot Projects Plasma Polypropylenes Publications Quality Control Research Research Personnel Resources Risk Factors Role Sampling Schedule Services Spinal Puncture Standardization System Technology Time Tube United States National Institutes of Health Vascular Cognitive Impairment Venipunctures Work assay development biobank cell injury cell type cerebral capillary cerebrovascular data dissemination data management experience improved in vitro Model induced pluripotent stem cell interest multiplex assay neurogenetics neurovascular unit novel open data pleiotrophin repository specific biomarkers statistics tau Proteins tau aggregation technology development three-dimensional modeling

项目摘要

CORE F – PROJECT SUMMARY/ABSTRACT The Biomarker Core (Core F) of the ADRC will provide services, resources and expertise in the vascular, blood- brain barrier (BBB), neurovascular unit (NVU) and standard Alzheimer’s disease (AD) amyloid-β (Aβ) and tau biomarkers for USC ADRC and outside investigators. This will support the central theme of our ADRC to elucidate vascular contributions to cognitive impairment and AD, and the role of cerebrovascular system, vascular and metabolic risk factors (VMRF), and NVU in cognitive decline and the pathogenesis of dementia and AD. The Biomarker Core F has expertise in developing novel vascular, BBB and NVU cell- and system-specific biomarkers in biofluids in addition to AD biomarkers (e.g., Aβ, tau, pTau). Core F will determine simultaneously in the cerebrospinal fluid (CSF) and plasma in participants of the primary ADRC vascular cohort study (VCS) biomarkers of vascular and BBB injury, other NVU biomarkers (e.g., astrocytes, microglia, inflammatory response, and neuronal injury) and AD Aβ, tau, and pTau biomarkers. Core F will also conduct Aβ and tau measurements and APOE genotyping in all ADRC participants that consent to CSF and/or blood collection. Existing strengths of our core include i) decades of experience and knowledge in studying the BBB, cerebrovascular system, and NVU; ii) experience in developing novel vascular/BBB biomarkers, as for example new, sensitive assays for novel analytes of interest including sPDGFRβ (pericyte injury marker), pleiotrophin (PTN, a growth factor expressed by brain capillary pericytes), cyclophilin A, ferritin, active TGF-β1, as well as Aβ and tau oligomer assays.; iii) providing reliable and simultaneous measurements of multiple NVU biomarkers in biofluids for all pilot data analyses of ADRC investigators using the ultrasensitive electrochemiluminescent Meso Scale Discovery (MSD) multiplex platform; and iv) on-going multi-year collaborations with several USC ADRC investigators including Drs. Chui, Toga, Harrington, Ringman, Wang, Nation, Yassine, Braskie, Pa, and others, and several external investigators working in the AD field (resulting in numerous publications). Core F will also generate and maintain a BioBank of peripheral blood mononuclear cells (PBMCs) to be sent and deposited to the NIH National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), and of induced pluripotent stem cells (iPSC) for ADRC investigators’ working on in vitro models of NVU, BBB and/or ‘brain on a chip’. Under the leadership of Dr. Zlokovic and the resources available at USC Zilkha Neurogenetic Institute, Core F will 1) coordinate and standardize biofluid collection, processing, storage and distribution; 2) assay CSF and plasma for vascular, BBB, NVU and standard AD biomarkers and conduct APOE genotyping; 3) provide technological developments; 4) generate and maintain a BioBank of PBMCs and iPSCs; and 5) facilitate data management, requests, and distribution to USC ADRC investigators to support our ADRC’s scientific goals. .

核心 F – 项目摘要/摘要 ADRC 的生物标记核心（核心 F）将提供血管、血液- 脑屏障 (BBB)、神经血管单位 (NVU) 和标准阿尔茨海默病 (AD) 淀粉样蛋白 (Aβ) 和 tau USC ADRC 和外部研究人员的生物标志物这将支持我们 ADRC 的中心主题：阐明血管对认知障碍和 AD 的影响，以及脑血管系统的作用，血管和代谢危险因素 (VMRF) 和 NVU 在认知能力下降和痴呆的发病机制中的作用 AD. Biomarker Core F 拥有开发新型血管、BBB 和 NVU 细胞和系统特异性的专业知识。除 AD 生物标志物（例如 Aβ、tau、pTau）外，还将同时测定生物体液中的生物标志物。主要 ADRC 血管队列研究 (VCS) 参与者的脑脊液 (CSF) 和血浆中血管和 BBB 损伤的生物标志物，其他 NVU 生物标志物（例如星形胶质细胞、小胶质细胞、炎症细胞）反应和神经损伤）和 AD Aβ、tau 和 pTau 生物标志物 Core F 也将传导 Aβ 和 tau。对所有同意脑脊液和/或血液采集的 ADRC 参与者进行测量和 APOE 基因分型。我们核心的现有优势包括 i) 数十年研究 BBB 的经验和知识，脑血管系统和 NVU；ii) 开发新型血管/BBB 生物标志物的经验，例如针对新型感兴趣的分析物进行新的灵敏检测，包括 sPDGFRβ（周细胞损伤标记物）、多效蛋白（PTN，一种由脑毛细血管周细胞表达的生长因子）、亲环蛋白 A、铁蛋白、活性 TGF-β1 以及 Aβ 和 tau 寡聚体测定。；iii) 提供多种 NVU 生物标志物的可靠且同步的测量 ADRC 研究人员使用超灵敏电化学发光 Meso 进行所有试点数据分析的生物流体 Scale Discovery (MSD) 多重平台；以及 iv) 与多个 USC ADRC 正在进行的多年合作研究人员包括 Chui 博士、Toga 博士、Harrington 博士、Ringman 博士、Wang 博士、Nation 博士、Yassine 博士、Braskie 博士、Pa 博士等，以及一些在 AD 领域工作的外部研究人员（产生了大量的出版物）。生成并维护外周血单核细胞 (PBMC) 的生物库，并将其发送并保存到 NIH 国家阿尔茨海默病和相关痴呆症中央存储库 (NCRAD) 以及诱导多能干细胞 (iPSC)，供 ADRC 研究人员研究 NVU、BBB 和/或的体外模型 “芯片上的大脑”在 Zlokovic 博士的领导下以及南加州大学 Zilkha 神经遗传学的可用资源研究所核心 F 将 1) 协调和标准化生物流体的收集、处理、储存和分配 2) 检测 CSF 和血浆的血管、BBB、NVU 和标准 AD 生物标志物并进行 APOE 基因分型 3)；提供技术发展；4) 生成和维护 PBMC 和 iPSC 生物库；5) 促进；数据管理、请求和分发给 USC ADRC 研究人员，以支持我们 ADRC 的科学目标。。