Biomarker Core

生物标志物核心

• 批准号: 10413836
• 负责人: LEONARD PETRUCELLI
• 金额: $ 28.6万
• 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/10413836
• 关键词: Alzheimer' s Disease; Biological Markers; Research

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.

生物标志物核心的总体目标是收集，库存和分发液体和细胞生物测量，以及 生成生物标志物数据集以解决异质性并改善阿尔茨海默氏病（AD）和 广告相关痴呆症（ADRD）。这样，生物标志物核心将与其他Mayo ADRC内核紧密合作 解决我们的整体主题，以研究“神经退行性疾病之间的相似性和差异”。期间 过去的资金周期，Mayo ADRC一直在改善诊断工具和定义方面处于最前沿 临床光谱包括正常衰老，临床前病理变化，轻度认知障碍（MCI）和 最终的疾病发作和进展。除了成像生物标志物外，我们的中心还在收集和 评估在包括血浆，血清和脑脊髓液（CSF）在内的生物测量中测量的生物标志物 定义痴呆症发展和进展过程的变化。进一步支持和加速 梅奥诊所和整个广泛研究社区的创新发现和翻译研究，我们 旨在建立这种新的生物标志物核心，以系统地融合并分发生物测量。我们也打算 生成和共享关键的生物标志物数据集，以实现研究努力，以定义早期的策略 AD/ADRD的诊断，预防和治疗。除了液体生物测量外，生物标志物核心还将 收集，库存和分发外周血单核细胞（PBMC）以及PBMC编程 诱导多能干细胞（IPSC）。生物标志物核心的这种创新元素将建立在现有的 通过Mayo Clinic神经代理实验室（MCNRL）的努力和专业知识，其中生物标志物核心 领导人Gujun Bu博士也担任董事。我们提出了生物标志物核心的四个特定目标。目标 1，我们计划从ADRC参与者的受试者中进行文献和分发血浆，血清和CSF样本 与临床核心协调，并将通过临床，神经影像学和 神经病理学核心。该目标的另一个活动是评估请求并通过 生物遇到委员会。在第二个目标中，我们计划生成并公开共享流体生物标志物数据集。 梅奥研究人员或 通过协作和核心服务。在AIM 3中，我们计划储存和分发用于蜂窝生物标志物的PBMC 发现和重新编程向IPSCS。在AIM 4中，我们将将选定的PBMC转换为IPSC进行银行业务， 分布和细胞生物标志物发现。将根据研究选择重编程的IPSC线 对AD/ADRD社区的兴趣，并将考虑捐助者的独特遗传背景（例如Apoe 和TREM2基因型）。除了向调查人员提供IPSC外，生物标志物核心还将提供 技术助理和培训IPSC与不同的脑细胞类型和脑器官的培训。 总之，这种全面而创新的生物标志物核心将成为Mayo ADRC的组成部分 为了发现和验证流体和细胞生物标志物。