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、储存和分发液体和细胞生物标本， 生成生物标志物数据集以解决异质性并改善阿尔茨海默病（AD）的诊断， AD相关性痴呆（ADRD）。在此过程中，生物标志物核心将与其他马约ADRC核心密切合作， 探讨“神经退化疾病的异同。期间 在过去的资助周期中，马约ADRC一直处于改进诊断工具和定义 临床谱包括正常衰老、临床前病理变化、轻度认知障碍（MCI）和 最终导致疾病发作和进展。除了成像生物标志物，我们的中心一直在收集和 评估生物样本（包括血浆、血清和脑脊液（CSF））中测量的生物标志物， 定义痴呆症发展和进展过程中的变化。为了进一步支持和加快 创新发现和转化研究在马约诊所和整个广泛的研究社区，我们 旨在建立这个新的生物标志物核心，以系统地储存和分发生物标本。我们还旨在 生成和共享关键的生物标志物数据集，以使研究工作能够为早期 AD/ADRD的诊断、预防和治疗。除了液体生物标本，生物标志物核心还将 收集、储存和分配外周血单核细胞（PBMC）以及PBMC重编程 诱导多能干细胞（iPSC）。生物标志物核心的这一创新元素将建立在现有的 通过马约诊所神经再生实验室（MCNRL）的努力和专业知识， 组长卜国军博士兼任主任。我们为生物标志物核心提出了四个具体目标。在Aim中 1，我们计划通过以下方式储存和分发ADRC参与者受试者的血浆、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。该目标的另一项活动是评估请求并通过一个 生物标本委员会。在第二个目标中，我们计划生成和虚拟共享流体生物标志物数据集。 血浆、血清和CSF中经验证的和新出现的生物标志物将由马约研究者或 通过合作和核心服务。在目标3中，我们计划储存和分发用于细胞生物标志物的PBMC 发现和重编程为iPSCs。在目标4中，我们将把选定的PBMC转化为iPSC用于储存， 分布和细胞生物标志物发现。将根据研究选择重新编程的iPSC系 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TREM 2基因型）。除了向研究人员提供iPSC外，生物标志物核心还将提供 为iPSC分化为不同的脑细胞类型和脑类器官提供技术援助和培训。 总之，这一全面和创新的生物标志物核心将成为马约ADRC的一个组成部分 从而能够发现和验证流体和细胞生物标志物。