Improved immunoprofiling to diagnose Alzheimer's Disease

改进免疫分析以诊断阿尔茨海默病

• 批准号: 6832129
• 负责人: Andrzej K Drukier
• 金额: $ 9.98万
• 依托单位: BIOTRACES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832129
• 关键词: Alzheimer' s disease; biomarker; brain disorder diagnosis; clinical research; cognition disorders; confocal scanning microscopy; cytokine; diagnosis design /evaluation; diagnosis quality /standard; disease /disorder prevention /control; early diagnosis; enzyme linked immunosorbent assay; fluorescence recovery after photobleaching; human tissue; inflammation; interferon gamma; interleukin 1; interleukin 18; interleukin 6; intermolecular interaction; macrophage inflammatory proteins; nerve growth factors; nuclear factor kappa beta; transcription factor; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is one of the most common and debilitating neurodegenerative diseases of older Americans. Several treatments show promise in slowing the development of AD, but to be truly effective, they must be started before full-blown AD appears. The prodominate phase of AD produces symptoms of mild cognitive impairment (MCI), but an ideal test would detect signs of incipient AD even before the appearance of MCI. Some recent data supports the view that inflammatory processes are important to the development of AD. We implemented a new technique, called Multiphoton Detection (MPD) supporting a family of high sensitivity diagnostic tests. In this application, MPD is used in assays targeting cytokines and applied to inflammatory processes leading to AD. The current assays are not sensitive enough to reliably measure cytokines in serum. We will demonstrate that the proposed protocols are sensitive and practical enough to be used as blood based screening assays for mild cognitive impairment (MCI) and AD. The specific aims of the proposed studies are: Aim 1: Further improvement of sensitivity of immunoassays for TNF-alpha, IFN-gamma, IL-1 beta and IL-6 Aim 2: Development of sub-pg/ml assay for IL-18 Aim 3: Optimization of ultrasensitive, CSF based assays of cytokines Aim 4: Validation of this assay by testing serum from MCI/AD patients and healthy controls.

描述（由申请人提供）：阿尔茨海默氏病（AD）是美国老年人最常见且最使人衰弱的神经退行性疾病之一。几种治疗方法有望减缓 AD 的发展，但要真正有效，必须在 AD 全面出现之前开始治疗。 AD 的主要阶段会产生轻度认知障碍 (MCI) 的症状，但理想的测试甚至可以在 MCI 出现之前检测出早期 AD 的迹象。最近的一些数据支持这样的观点：炎症过程对于 AD 的发展很重要。 我们实施了一种称为多光子检测 (MPD) 的新技术，支持一系列高 敏感性诊断测试。在此应用中，MPD 用于针对细胞因子的检测，并应用于导致 AD 的炎症过程。目前的检测方法不够灵敏，无法可靠地测量血清中的细胞因子。我们将证明所提出的方案足够灵敏且实用，足以用作轻度认知障碍 (MCI) 和 AD 的血液筛查测定。拟议研究的具体目标是： 目标 1：进一步提高 TNF-α、IFN-γ、IL-1β 和 IL-6 免疫测定的灵敏度 目标 2：开发亚 pg/ml IL-18 检测方法 目标 3：优化超灵敏、基于 CSF 的细胞因子测定 目标 4：通过测试 MCI/AD 患者和健康对照的血清来验证该测定法。