Biomarker Core

核心F--项目摘要/摘要 ADRC的生物标志物核心(核心F)将提供血管、血液和血液领域的服务、资源和专业知识。 脑屏障、神经血管单位和标准阿尔茨海默病淀粉样蛋白β(Aβ)和tau 南加州大学ADRC和外部调查人员的生物标志物。这将支持我们亚洲发展研究委员会的中心主题 阐明血管在认知障碍和AD中的作用，以及脑血管系统的作用， 血管和代谢危险因子(VMRF)、NVU与认知功能减退和痴呆的发病机制 广告。Biomarker Core F在开发针对细胞和系统的新型血管、血脑屏障和NVU方面拥有专业知识 生物体液中的生物标记物以及AD生物标记物(例如，Aβ、tau、ptau)。核心F将同时确定 在最初的ADRC血管队列研究(VCS)参与者的脑脊液和血浆中 血管和血脑屏障损伤的生物标记物，其他NVU生物标记物(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生物标记物。核心F还将进行Aβ和Tau 对所有同意脑脊液和/或采血的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)在研究BBB方面有数十年的经验和知识， 脑血管系统和NVU；ii)开发新的血管/血脑屏障生物标志物的经验，例如 新的、敏感的检测新的感兴趣的分析物，包括sPDGFRβ(周细胞损伤标记物)、多营养素 (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、活性转化生长因子-β1以及A-β 和tau寡聚体分析；iii)提供可靠和同时测量多个NVU生物标志物 使用超灵敏电致化学发光介质法分析ADRC研究人员所有试点数据的生物流体 规模发现(MSD)多路传输平台；以及iv)与几个南加州大学ADRC持续多年的合作 调查人员包括崔博士、托加博士、哈林顿博士、林曼博士、王博士、Nation博士、亚辛博士、Braskie博士、PA博士等， 以及在广告领域工作的几名外部调查人员(出版了许多出版物)。核心F也将 生成和维护外周血单个核细胞(PBMC)生物库，以发送和存放到 美国国立卫生研究院阿尔茨海默病及相关痴呆国家中央资料库(NCRAD) ADRC研究人员用于NVU、BBB和/或体外模型研究的诱导多能干细胞(IPSC) “脑洞大开”。在Zlokovic博士和南加州大学Zilkha Neurogenic现有资源的领导下 研究所，核心F将1)协调和标准化生物液的收集、加工、储存和分配；2) 检测脑脊液和血浆中血管、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)建立和维护PBMC和IPSC生物库；以及5)促进 数据管理、请求和分发给南加州大学ADRC调查人员，以支持我们ADRC的科学目标。 。

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. .