Biomarker Core

摘要-生物标志物核心 新配置的生物标志物核心（BC）的主要目标是收集、储存和分配生物流体， 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 认知功能减退（SCD）、轻度认知功能障碍（MCI）和阿尔茨海默病（AD）早期， 长期目标是开发新的干预措施，以延迟或防止这些转变。在其超过 25年的持续资助，纽约大学ADRC一直处于改善诊断工具和定义 AD的临床前和前驱期。在此更新期间，将对专用BC进行重新配置， 一个概念和技术核心，为既定的调查人员和下一代的学生， 神经科学家;以及，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，以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液体的摄入、处理和储存 核心（CC）参与者与数据管理和统计（DMS）核心。在目标2中，我们 对已知的血液和CSF生物标志物进行最先进的分析，用于诊断、预后和预测 的AD。检测将包括但不限于Aβ40/42/38、磷酸化/总tau和神经丝 轻链，都在新的淀粉样蛋白/tau/神经变性（ATN）框架内，除了标记物 脑血管疾病、炎症、神经胶质活化，以及生物学变量如年龄、性别、ApoE 4， 和睡眠（以及其他），这将是增加我们对疾病异质性理解的关键。在目标3中， 我们将使用Simoa技术开发新的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）核心的发现和来自ADRC网络的其他新兴数据。Aim 4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、神经成像（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， 纽约大学内部的其他研究合作工作（例如纽约大学代谢组学实验室）和来自以下方面的外部合作者 其他ADRC（例如微生物组项目）。最后，在目标6中，我们将与其他发展成果中心合作， 优化各中心的生物标志物检测。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核心合作，帮助了解疾病 异质性和向SCD、MCI和AD的阶段转换。此外，它将有助于协调多种生物标志物 分析和开发新的AD超灵敏生物标志物的科学发现。

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.