Biomarker Core

生物标志物核心

• 批准号: 10247459
• 负责人: Berislav V Zlokovic
• 金额: $ 43.82万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 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/10247459
• 关键词: Aliquot; Alzheimer' s Disease; Alzheimer' 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; Development; 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; Institutes; Knowledge; Leadership; Measurement; Metabolic; Microglia; Neuronal Injury; 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; 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; three-dimensional modeling

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 -项目总结/摘要 ADRC的生物标志物核心（核心F）将提供血管、血液和心血管领域的服务、资源和专业知识。 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-β（Aβ）和tau蛋白 USC ADRC和外部研究者的生物标志物。这将支持我们的ADRC的中心主题， 阐明血管对认知障碍和AD的贡献，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， AD.生物标志物核心F在开发新型血管、BBB和NVU细胞和系统特异性 生物流体中的生物标志物除了AD生物标志物（例如，Aβ、tau、pTau）。核心F将同时确定 主要ADRC血管队列研究（ADRC）受试者的脑脊液（CSF）和血浆中 血管和BBB损伤的生物标志物，其它NVU生物标志物（例如，星形胶质细胞，小胶质细胞，炎性 反应和神经元损伤）和AD Aβ、tau和pTau生物标志物。核心F还将进行Aβ和tau 在所有同意CSF和/或血液采集的ADRC参与者中进行APOE测量和基因分型。 我们核心的现有优势包括i）数十年研究BBB的经验和知识， ii）开发新的血管/BBB生物标志物的经验，例如 新的、灵敏的检测方法，用于检测新的目标分析物，包括sPDGFRβ（周细胞损伤标志物）、多效生长因子 (PTN一种由脑毛细血管周细胞表达的生长因子）、亲环素A、铁蛋白、活性TGF-β1以及Aβ 和tau寡聚体测定。iii）提供多种NVU生物标志物的可靠和同时测量， ADRC研究人员使用超灵敏电致发光Meso 规模发现（MSD）多路复用平台;以及iv）与几个南加州大学ADRC正在进行的多年合作 调查人员包括崔博士、托加博士、哈灵顿博士、林曼博士、王博士、国家博士、亚辛博士、布拉斯基博士、帕博士和其他人， 以及在反倾销领域工作的几位外部调查员（导致大量出版物）。核心F还将 生成并维持外周血单核细胞（PBMC）的生物库，以发送并储存到 美国国立卫生研究院阿尔茨海默病和相关痴呆症国家集中储存库（NCRAD），以及 诱导多能干细胞（iPSC）用于ADRC研究人员在NVU，BBB和/或 “芯片大脑”在Zlokovic博士的领导下，利用南加州大学Zilkha神经遗传学的资源， 研究所，核心F将1）协调和标准化生物流体收集，处理，储存和分配; 2） 测定CSF和血浆中的血管、BBB、NVU和标准AD生物标志物，并进行APOE基因分型; 3） 提供技术开发; 4）生成和维护PBMC和iPSC的生物库;以及5）促进 数据管理，请求和分发给USC ADRC调查人员，以支持我们ADRC的科学目标。 .