Project 1 Biomarkers

项目1 生物标志物

• 批准号: 10408060
• 负责人: PAUL F WORLEY
• 金额: $ 28.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408060
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Biological Assay; Biological Markers; Biology; Blood; Blood specimen; Brain; Chronic; Clinical; Clinical Trials; Cognition; Cognitive; Complement 1q; Cross-Sectional Studies; Data; Diagnostic; Discrimination; Disease; Enzyme-Linked Immunosorbent Assay; Excitatory Synapse; Experimental Designs; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hippocampus (Brain); Human; Impaired cognition; Individual; Inflammation; Inflammation Mediators; Inflammatory; Interleukin-6; Interneurons; Link; Magnetic Resonance Imaging; Measures; Mediating; Methods; Neocortex; Neurobiology; Participant; Pathway interactions; Performance; Phase; Prevention strategy; Process; Proteins; Research; Rest; Sampling; Symptoms; Synapses; TNF gene; Testing; Time; Western Blotting; base; cognitive change; cognitive performance; cognitive testing; cohort; entorhinal cortex; exosome; improved; inflammatory marker; insight; metabolomics; mild cognitive impairment; pre-clinical; receptor; relating to nervous system; synaptic function; systemic inflammatory response; tau Proteins; tau-1; treatment response; treatment strategy

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.

项目1：摘要/摘要 项目1的目标是“临床前广告的突触和炎症标记”的目标是检查几个 与突触功能和全身性炎症有关的新措施，以确定其作为生物标志物的价值 用于临床前广告。这些分析将使用纵向收集的CSF和Biocard的血液标本 参与者评估这些措施。对于合成标记，有两个主要目的：（1）到 测量NPTX2，一种突触蛋白和相关标记的NPTX1和NPTXR，并检查其 与先前在生物卡参与者中收集的临床，认知和生物标志物数据的关系； （2）检查一种基于血液的测定，该测定法测量NPTX2和神经外泌体中相关蛋白 从血液中分离出来，并确定它是否与从CSF获得的可比措施有类似的关联。 对于炎症标记，有两个主要目的：（1）测量3个关键炎症生物标志物 在血液（IL-6，TNFR1和CRP）中，并检查它们与临床，认知和生物标志物数据的关系 以前收集在生物卡参与者中； （2）进行有针对性的探索性代谢组学 在血液和CSF样品中进行分析，以识别可能参与的炎症途径 临床前广告。总体而言，这些研究将确定这些突触和炎症标记的变化是否 在临床前广告期间，可以提供有关测量的见解，这些测量可能对临床前AD的临床试验有用 （即，要么选择在临床试验中包括的受试者，要么在临床中跟踪对治疗的反应 试验）和/或提供有关在此期间不断发展的基本神经生物学过程的见解 AD的临床前阶段。