Project 1 Biomarkers

项目1：摘要/摘要 项目1的目标是检查几个临床前AD的突触和炎症标记物 与突触功能和全身炎症相关的新指标，以确定它们作为生物标志物的价值 用于临床前AD。这些分析将使用从BIOCARD纵向收集的脑脊液和血液样本 参与者对这些措施进行评估。对于突触标志物，主要有两个目的：(1) 检测脑脊液中突触蛋白NPTX2及相关标志物NPTX1和NPTXR，并检测其 与以前在BIOCARD参与者中收集的临床、认知和生物标记物数据的关系； 以及(2)检验一种基于血液的检测神经外显体中NPTX2和相关蛋白质的方法 从血液中分离出来，并确定它是否与从脑脊液中获得的可比指标具有类似的相关性。 对于炎症标志物，主要有两个目标：(1)测量3个关键的炎症生物标志物 并检查它们与临床、认知和生物标记物数据的关系 以前在BIOCARD参与者中收集的数据；以及(2)进行有针对性的探索性代谢组学 血液和脑脊液样本的分析，以确定可能参与的炎症途径 临床前AD。总体而言，这些研究将确定这些突触和炎症标志物的变化 在临床前AD期间，可以提供对临床前AD临床试验可能有用的措施的见解 (即，用于选择要包括在临床试验中的受试者或用于跟踪临床试验中的治疗反应 试验)，和/或提供对潜在神经生物学过程的洞察 阿尔茨海默病临床前期。

PROJECT 1: SUMMARY/ABSTRACT The goal of Project 1, entitled ‘Synaptic and Inflammatory Markers for Preclinical AD’ is to examine several new measures related to synaptic function and systemic inflammation to determine their value as biomarkers for preclinical AD. These analyses will use longitudinally collected CSF and blood specimens from BIOCARD participants to evaluate these measures. For the synaptic markers, there are two primary aims: (1) to measure NPTX2, a synaptic protein, and related markers NPTX1 and NPTXR in CSF, and examine their relationship with the clinical, cognitive and biomarker data previously collected in the BIOCARD participants; and (2) to examine a blood-based assay that measures NPTX2 and related proteins in neural exosomes isolated from blood and determine if it has a similar association with comparable measures obtained from CSF. For the inflammatory markers, there are two primary aims: (1) to measure 3 key inflammatory biomarkers in blood (IL-6, TNFR1, and CRP) and examine their relationship with the clinical, cognitive and biomarker data previously collected in the BIOCARD participants; and (2) to conduct targeted exploratory metabolomic analyses in both blood and CSF samples, in order to identify inflammatory pathways that may be involved in preclinical AD. Overall, these studies will determine if the changes in these synaptic and inflammatory markers during preclinical AD can provide insights into measures that might be useful for a clinical trial in preclinical AD (i.e., for either selecting subjects to include in a clinical trial or for tracking response to treatment in a clinical trial), and/or provide insights into the underlying neurobiological processes that are evolving during the preclinical phase of AD.