Biomarker Core

生物标志物核心

• 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
• 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' 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; 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

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的生物标志物核心（核心F）将在血管，血液中提供服务，资源和专业知识 脑屏障（BBB），神经血管单元（NVU）和标准阿尔茨海默氏病（AD）淀粉样蛋白β（Aβ）和TAU USC ADRC和外部调查人员的生物标志物。这将支持我们的ADRC的中心主题 阐明对认知障碍和AD的血管贡献，以及脑血管系统的作用， 血管和代谢危险因素（VMRF）和NVU在认知下降以及痴呆和发病机理中 广告。生物标志物核F具有开发新型血管，BBB和NVU细胞和系统特异性方面的专业知识 除了AD生物标志物（例如Aβ，TAU，PTAU）外，生物流体中的生物标志物。核心F将简单地确定 在原发性ADRC血管队列研究（VCS）的参与者中，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 反应，神经元损伤）和ADAβ，TAU和PTAU生物标志物。核F还将进行Aβ和TAU 同意CSF和/或收集血液的所有ADRC参与者中的测量和APOE基因分型。 我们核心的现有优势包括i）研究BBB数十年的经验和知识， 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 新的，敏感的测定方法，用于新的感兴趣分析物，包括SPDGFRβ（Pericyte损伤标记），Pleiotiotirophin （PTN，由脑毛细管周细胞表达的生长因子），环磷脂A，铁蛋白，活性TGF-β1以及Aβ 和Tau低聚物测定法。 iii）在多种NVU生物标志物中提供可靠和同时测量 使用超敏电化学发光中等的ADRC研究者的所有试验数据分析的生物流体 比例发现（MSD）多路复用平台；和iv）与多个USC ADRC进行的多年合作 调查人员在内。 Chui，Toga，Harrington，Ringman，Wang，Nation，Yassine，Braskie，PA等 以及在广告领域工作的一些外部研究人员（导致许多出版物）。核心F也将 生成并维护外周血单核细胞（PBMC）的生物库 NIH国家集中式阿尔茨海默氏病和相关痴呆症（NCRAD）和 用于ADRC研究人员的NVU，BBB和/或的诱导多能干细胞（IPSC）。 “大脑在芯片上”。在Zlokovic博士的领导下以及USC Zilkha神经源的资源 Institute，Core F Will 1）协调和标准化生物流体收集，处理，存储和分配； 2） 用于血管，BBB，NVU和标准AD生物标志物的CSF和血浆分析并进行APOE基因分型； 3） 提供技术发展； 4）生成和维持PBMC和IPSC的生物库； 5）便利 数据管理，请求和向USC ADRC调查人员分发，以支持我们的ADRC的科学目标。 。