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 广告。 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 生物标志物外，生物体液中的生物标志物（例如 Aβ、tau、pTau）。核心F将同时确定 主要 ADRC 血管队列研究 (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） 反应和神经元损伤）和 AD Aβ、tau 和 pTau 生物标志物。 Core F 还将传导 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 寡聚体检测。 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； iv) 与几个 USC ADRC 正在进行的多年合作 研究人员，包括博士。 Chui、Toga、Harrington、Ringman、Wang、Nation、Yassine、Braskie、Pa 等， 以及几位在 AD 领域工作的外部研究人员（发表了大量出版物）。核心F也将 生成并维护外周血单核细胞 (PBMC) 的生物库，并将其发送并存入 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 USC Zilkha Neurogenic 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） 检测脑脊液和血浆中的血管、BBB、NVU 和标准 AD 生物标志物，并进行 APOE 基因分型； 3） 提供技术发展； 4) 生成并维护 PBMC 和 iPSC 的生物库； 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。 。