Biomarker Core

生物标志物核心

• 批准号: 10657563
• 负责人: LEONARD PETRUCELLI
• 金额: $ 31.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10657563
• 关键词: 3-Dimensional; Acceleration; Address; Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-42; Apolipoprotein E; Astrocytes; Biological Assay; Biological Markers; Biological Specimen Banks; Blood; Blood Cells; Brain; Brain imaging; C9ORF72; CCL2 gene; Cell Line; Cell model; Cells; Cerebrospinal Fluid; Clinic; Clinical; Clinical Data; Clinical assessments; Collaborations; Collection; Communities; Data; Data Set; Dementia; Deposition; Development; Disease; Disease Progression; Disease model; Drug Screening; Early Diagnosis; Education; Elements; Endothelial Cells; Epigenetic Process; Evaluation; Florida; Functional disorder; Funding; Generations; Genetic; Genotype; Goals; Heterogeneity; Human; Image; Immune; Individual; Infrastructure; Knowledge; Link; Liquid substance; Measures; Microglia; Modeling; Nerve Regeneration; Neurodegenerative Disorders; Neurons; Onset of illness; Organoids; Participant; Pathologic; Patients; Peripheral; Peripheral Blood Mononuclear Cell; Plasma; Prevention; Process; Property; Protocols documentation; Research; Research Personnel; Sampling; Serum; Services; Site; TREM2 gene; Technology; Testing; Therapeutic Intervention; Training; Translational Research; Validation; Work; alpha synuclein; assay development; biomarker discovery; brain cell; cell bank; cell type; data sharing; diagnostic tool; disease diagnosis; drug testing; imaging biomarker; improved; induced pluripotent stem cell; innovation; interest; mild cognitive impairment; neurofilament; neurogranin; neuroimaging; neuropathology; normal aging; pre-clinical; public database; synergism; tau Proteins; tau-1; therapeutic evaluation

The overall goal of the Biomarker Core is to collect, bank, and distribute fluid and cellular biospecimens and generate biomarker datasets to address heterogeneity and improve diagnosis for Alzheimer’s disease (AD) and AD-related dementias (ADRD). In doing so, the Biomarker Core will work closely with other Mayo ADRC Cores to address our overall theme to study the “similarities and differences among neurodegenerative diseases”. During the past funding cycles, the Mayo ADRC has been in the forefront in improving diagnostic tools and defining clinical spectrum including normal aging, preclinical pathological changes, mild cognitive impairment (MCI), and ultimately disease onset and progression. In addition to imaging biomarkers, our center has been collecting and evaluating biomarkers measured in biospecimens including plasma, serum, and cerebral spinal fluid (CSF) to define changes in the course of dementia development and progression. To further support and accelerate the innovative discovery and translational research at Mayo Clinic and across the broad research community, we aim to establish this new Biomarker Core to systematically bank and distribute biospecimens. We also aim to generate and share critical biomarker datasets to enable research efforts in defining strategies for the early diagnosis, prevention and treatment of AD/ADRD. In addition to fluid biospecimens, the Biomarker Core will also collect, bank and distribute peripheral blood mononuclear cells (PBMCs), as well as PBMC-reprogrammed induced pluripotent stem cells (iPSCs). This innovative element of the Biomarker Core will built upon existing efforts and expertise through the Mayo Clinic Neuroregeneration Lab (MCNRL) where the Biomarker Core Leader Dr. Guojun Bu also serves as the Director. We propose four Specific Aims for the Biomarker Core. In Aim 1, we plan to bank and distribute plasma, serum and CSF samples from ADRC participants subjects by coordinating with the Clinical Core, and link sample information obtained through the Clinical, Neuroimaging, and Neuropathology Cores. Another activity of this Aim is to evaluate requests and distribute biospecimens through a Biospecimen Committee. In the second Aim, we plan to generate and publically share fluid biomarker datasets. Both validated and emerging biomarkers in plasma, serum and CSF will be measured by Mayo investigators or through collaboration and core services. In Aim 3, we plan to bank and distribute PBMCs for cellular biomarker discovery and for reprogramming to iPSCs. In Aim 4, we will convert selected PBMCs to iPSCs for banking, distribution and cellular biomarker discover. The reprogrammed iPSC lines will be selected based on research interests in the AD/ADRD community and will consider unique genetic backgrounds of the donors (e.g., APOE and TREM2 genotype). In addition to supplying iPSCs to investigators, the Biomarker Core will also provide technical assistant and training for differentiation of iPSCs to different brain cell types and brain organoids. Together, this comprehensive and innovative Biomarker Core will become an integral component of Mayo ADRC to enable the discovery and validation of fluid and cellular biomarkers.

Biomarker Core的总体目标是收集、储存和分发液体和细胞生物显微镜以及 生成生物标记物数据集以解决异质性并改进阿尔茨海默病(AD)的诊断和 AD相关痴呆(ADRD)。在这样做的过程中，Biomarker Core将与其他Mayo ADRC核心密切合作，以 讲解我们研究“神经退行性疾病之间的异同”的总主题。在.期间 在过去的资金周期中，梅奥亚洲发展研究中心在改进诊断工具和确定 临床范围包括正常衰老、临床前病变、轻度认知障碍(MCI)和 最终导致疾病的发生和发展。除了成像生物标记物，我们的中心一直在收集和 评估生物标记物包括血浆、血清和脑脊液(CSF)中测量的生物标记物 定义痴呆症发展和进展过程中的变化。进一步支持和加快 梅奥诊所和整个研究社区的创新发现和转化研究，我们 目的建立这一新的生物标记物核心，系统地储存和分配生物标记物。我们的目标还包括 生成和共享关键生物标记物数据集，以支持制定早期战略的研究工作 AD/ADRD的诊断与防治除了流体生物标记物外，Biomarker Core还将 收集、储存和分发外周血单核细胞(PBMC)以及重新编程的PBMC 诱导多能干细胞(IPSCs)。Biomarker核心的这一创新元素将建立在现有的 通过梅奥临床神经再生实验室(MCNRL)的努力和专业知识，其中Biomarker Core 院长卜国军博士兼任主任。我们为Biomarker Core提出了四个具体目标。在AIM 1，我们计划通过以下方式储存和分发ADRC参与者的血浆、血清和脑脊液样本 与临床核心协调，并将通过临床、神经成像和 神经病理学核心。这一目标的另一项活动是评估请求并通过 生物质学家委员会。在第二个目标中，我们计划生成并公开共享流体生物标记物数据集。 血浆、血清和脑脊液中经过验证的和新出现的生物标记物将由Mayo调查人员或 通过协作和核心服务。在目标3中，我们计划储存和分配PBMC作为细胞生物标记物 发现和重新编程到iPSC。在目标4中，我们将选定的PBMC转换为IPSC用于银行业务， 分布和细胞生物标记物的发现。重新编程的IPSC系列将根据研究结果进行选择 AD/ADRD社区的利益，并将考虑捐赠者的独特遗传背景(例如，APOE 和TREM2基因)。除了向调查人员提供IPSC外，Biomarker Core还将提供 IPSCs分化为不同脑细胞类型和脑器官的技术援助和培训。 总而言之，这一全面而创新的Biomarker Core将成为梅奥ADRC不可或缺的组成部分 以实现流体和细胞生物标记物的发现和验证。