Developing EV surface proteins as biosignatures for Alzheimer's disease (AD)

开发 EV 表面蛋白作为阿尔茨海默病 (AD) 的生物特征

• 批准号: 9908966
• 负责人: W. Andy Tao
• 金额: $ 24.49万
• 依托单位: TYMORA ANALYTICAL OPERATIONS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908966
• 关键词: Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer’s disease biomarker; American; Benchmarking; Biological Assay; Biological Markers; Blood; Blood Tests; Body Fluids; Brain; Cell physiology; Cells; Chronic; Clinical; Clinical Research; Collection; Communication; Consensus; Cytolysis; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Digestion; Disease; Disease Management; Disease Marker; Disease Progression; Early Diagnosis; Endocannabinoids; Ensure; Enzymes; Future; Genome; In Situ; Literature; Mass Spectrum Analysis; Measures; Medical; Membrane Proteins; Methods; MicroRNAs; Monitor; Nature; Nerve Degeneration; Neurons; Organism; Output; Patients; Phase; Physiological; Plasma; Preparation; Procedures; Protein Analysis; Proteins; Recovery; Reproducibility; Research; Resolution; Sampling; Signaling Molecule; Small Business Technology Transfer Research; Source; Symptoms; Synaptic plasticity; Techniques; Technology; Therapeutic; Time; United States National Institutes of Health; Urine; Validation; Vesicle; Work; base; biomarker discovery; biomarker validation; biosignature; blood-brain barrier crossing; brain tissue; diagnostic biomarker; disease diagnosis; extracellular vesicles; human subject; innovation; link protein; mild cognitive impairment; minimally invasive; novel; novel strategies; receptor; therapeutic target; vesicle transport

PROJECT SUMMARY The rising number of Americans currently living with Alzheimer’s disease (AD) demands pressing therapeutic and diagnostic solutions. The consensus is that early detection is critical to delay and better manage the disease. The recent discovery of extracellular vesicles (EVs) and their potentially important cellular functions in neuronal-glial communication, synaptic plasticity, or as endocannabinoid carriers has presented them as intriguing sources for neuronal disease diagnosis and therapeutics. The growing body of functional studies have provided strong evidence that EV-based disease markers, such as active miRNAs and signaling molecules, can be identified well before the onset of symptoms or physiological detection of diseases, making them a promising source for early-stage AD detection. However, multiple technical challenges related to EV-based biomarker discovery have greatly limited its applications in clinical studies. In this STTR study that focuses on innovative EV research and detection for AD, we will apply a novel strategy for EV isolation and analysis, rigorously characterize disease-relevant EV surface proteins, and then focus on developing EV surface proteins as biosignatures for AD. EV surface proteins, consisting of receptors, transporters, channels, and enzymes, are a source of potential diagnostic biomarkers of disease and therapeutic targets. More importantly, the detection of EV surface proteins can be achieved in situ without long sample preparation procedure such as lysis, protein extraction, digestion, enrichment and so on. The proposed strategy introduces a novel platform technology for EV isolation and on-bead detection of EV surface proteins specific to AD. Accordingly, the following aims will be completed: Aim #1: Implementation of an integrated strategy for fast and effective EV isolation and cargo extraction; Aim #2: Characterization of EV surface proteins linked to AD; Aim #3: Development of on-bead detection of EV surface proteins as biosignatures for AD. By the completion of this exploratory project, we expect to establish a platform technology to detect EV surface proteins as promising AD biomarkers for further validation.

项目摘要 目前患有阿尔茨海默氏病（AD）的美国人数量增加了 治疗和诊断解决方案。共识是，早期检测对于延迟至关重要 更好地管理疾病。最近发现细胞外蔬菜（EV）及其潜在的发现 神经元通信，突触可塑性或AS中的重要细胞功能 内源性大麻素载体已将其作为神经元疾病诊断的有趣来源 和治疗。越来越多的功能研究已经提供了有力的证据表明 可以很好地鉴定出基于EV的基于EV的疾病标志物，例如活性miRNA和信号分子 症状发作或疾病的身体发现之前，使其成为诺言 早期广告检测的来源。但是，与基于EV有关的多个技术挑战 生物标志物发现极大地限制了其在临床研究中的应用。在这项STTR研究中 专注于AD的创新电动汽车研究和检测，我们将采用EV的新型策略 隔离和分析，严格表征与疾病相关的EV表面蛋白，然后聚焦 开发EV表面蛋白作为AD的生物签名。 EV表面蛋白，由 受体，转运蛋白，通道和酶是潜在的诊断生物标志物的来源 疾病和治疗靶标。更重要的是，可以检测EV表面蛋白 在没有长期样品制备程序的原位实现，例如裂解，蛋白质提取， 消化，富集等。拟议的策略介绍了一种新颖的平台技术 EV分离和对AD特异的EV表面蛋白的珠子检测。根据以下内容 目标将完成：目标＃1：实施快速有效的EV的集成策略 隔离和提取货物；目标＃2：与AD相关的EV表面蛋白的表征； AIM＃3： 开发对EV表面蛋白作为AD的生物签名的珠子上检测。完成 在这个探索性项目中，我们希望建立一种平台技术来检测电动汽车表面蛋白 作为有前途的广告生物标志物，以进一步验证。