Biomarker Core

生物标志物核心

• 批准号: 10643943
• 负责人: THOMAS M WISNIEWSKI
• 金额: $ 24.25万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643943
• 关键词: Address; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Basic Science; Biological; Biological Assay; Biological Markers; Blood; Blood Vessels; Brain; Cerebrospinal Fluid; Cerebrovascular Disorders; Clinical; Clinical Research; Cognitive; Collaborations; Communities; DNA; DNA Methylation; Data; Data Set; Dedications; Dementia; Diagnosis; Disease; Disease Progression; Enzyme-Linked Immunosorbent Assay; Equipment; Fostering; Funding; Future; Genomics; Goals; Heterogeneity; Human Resources; Impaired cognition; Inflammation; Intake; Interdisciplinary Study; Intervention; Light; Link; Magnetic Resonance Imaging; Nerve Degeneration; Participant; Pathology; Pathway interactions; Phosphorylation; Plasma; Positron-Emission Tomography; Postdoctoral Fellow; Procedures; Process; Prognosis; Proteomics; Quality Control; RNA; Research; Research Personnel; Risk; Role; Sampling; Scientific Advances and Accomplishments; Serum; Sleep; Students; Systems Biology; Technology; Tissue Banks; Translational Research; Work; apolipoprotein E-4; behavior measurement; clinically relevant; cost effective; data management; data sharing; design; diagnostic tool; disease heterogeneity; epidemiology study; glial activation; improved; metabolomics; microbiome; microbiome analysis; mild cognitive impairment; neurobiological mechanism; neurofilament; neuroimaging; neuropathology; next generation; normal aging; novel; novel marker; phenotypic biomarker; pre-clinical; predictive modeling; prevent; programs; sex; statistics; stool sample; tau Proteins; tau-1; tool; transcriptomics

ABSTRACT – BIOMARKER CORE The primary objective of the newly configured Biomarker Core (BC) is to collect, bank, and distribute biofluids in order to generate biomarker datasets that will address disease heterogeneity and clinical transitions to subjective cognitive decline (SCD), mild cognitive impairment (MCI) and early stages of Alzheimer's disease (AD), with the long term goal of developing novel interventions that will delay or prevent these transitions. During its more than 25 years of continued funding, the NYU ADRC has been in the forefront of improving diagnostic tools and defining preclinical and prodromal stages of AD. In this renewal period, the dedicated BC will be reconfigured to serve as a conceptual and technical core for established investigators and the next generation of students and neuroscientists; and, to foster the use of plasma, serum and cerebrospinal fluid (CSF), as well as stool samples for microbiome analyses, to understand biological mechanisms of disease progression and heterogeneity. We propose the following Aims. In Aim 1, we will coordinate intake, processing and storage of biofluids from Clinical Core (CC) participants in association with the Data Management & Statistics (DMS) Core. In Aim 2, we will perform state-of-the-art analysis of known blood and CSF biomarkers for the diagnosis, prognosis, and prediction of AD. Assays will include, but will not be limited to, Aβ40/42/38, phosphorylated/total tau and neurofilament light-chain, all within the new amyloid/tau/neurodegeneration (ATN) framework, in addition to markers of cerebrovascular disease, inflammation, glial activation, as well as biological variables such as age, sex, ApoE4, and sleep (among others), which will be key to increase our understanding of disease heterogeneity. In Aim 3, we will use Simoa technology to develop novel ultrasensitive biomarker assays, guided in part by proteomic findings by the Neuropathology (NP) Core and other emerging data from the ADRC network. Aim 4 is designed to manage samples, perform quality control and analyses as well as link sample information obtained through the DMS, CC, Neuroimaging (NIC), and NP Cores. As part of Aim 5, we will share biosamples with NCRAD and other research collaborative efforts within NYU (e.g. NYU Metabolomics Lab) and outside collaborators from other ADRC (e.g. Microbiome Project). Last, in Aim 6, we will collaborate with other ADRCs to harmonize and optimize biomarker assays across centers. In summary, the BC will perform state-of-the-art biofluid biomarker analyses within the new ATN framework, and work with the NIC and CC cores to help understand disease heterogeneity and stage transitions to SCD, MCI, and AD. Further, it will help harmonize multiple biomarker assays and develop scientific discovery of novel ultrasensitive biomarkers for AD.

摘要 – 生物标志物核心 新配置的生物标记核心 (BC) 的主要目标是收集、储存和分配生物体液 为了生成生物标志物数据集，以解决疾病异质性和临床向主观转变的问题 认知衰退（SCD）、轻度认知障碍（MCI）和阿尔茨海默病（AD）的早期阶段， 制定新的干预措施来延迟或阻止这些转变的长期目标。在其超过 25 年来持续资助，纽约大学 ADRC 一直走在改进诊断工具和定义 AD 的临床前和前驱阶段。在本次更新期间，专用BC将被重新配置为 为现有研究人员和下一代学生提供概念和技术核心 神经科学家；促进血浆、血清和脑脊液 (CSF) 以及粪便样本的使用 用于微生物组分析，了解疾病进展和异质性的生物学机制。我们 提出以下目标。在目标 1 中，我们将协调临床生物体液的摄入、处理和储存 与数据管理和统计 (DMS) 核心相关的核心 (CC) 参与者。在目标 2 中，我们将 对已知的血液和脑脊液生物标志物进行最先进的分析，以进行诊断、预后和预测 公元。检测包括但不限于 Aβ40/42/38、磷酸化/总 tau 和神经丝 轻链，全部位于新的淀粉样蛋白/tau/神经退行性变 (ATN) 框架内，此外还有 脑血管疾病、炎症、神经胶质活化，以及年龄、性别、ApoE4等生物学变量， 和睡眠（除其他外），这将是增加我们对疾病异质性的理解的关键。在目标 3 中， 我们将使用 Simoa 技术开发新型超灵敏生物标志物检测，部分由蛋白质组学指导 神经病理学 (NP) 核心的发现和 ADRC 网络的其他新数据。目标4已设计 管理样品、执行质量控制和分析以及链接通过以下方式获得的样品信息 DMS、CC、神经影像 (NIC) 和 NP 核心。作为目标 5 的一部分，我们将与 NCRAD 共享生物样本 纽约大学内部（例如纽约大学代谢组学实验室）和外部合作者的其他研究合作努力 其他 ADRC（例如微生物组项目）。最后，在目标 6 中，我们将与其他 ADRC 合作，协调和协调 优化跨中心的生物标志物测定。总之，BC 将进行最先进的生物流体生物标志物 在新的 ATN 框架内进行分析，并与 NIC 和 CC 核心一起帮助了解疾病 异质性以及向 SCD、MCI 和 AD 的阶段过渡。此外，它将有助于协调多种生物标志物 检测并开发新型超灵敏 AD 生物标志物的科学发现。