Multiplexed point-of-care testing for inflammatory miRNA and neurotransmitter profiling in Alzheimer’s disease diagnostics

阿尔茨海默病诊断中炎症 miRNA 和神经递质分析的多重即时检测

• 批准号: 421356369
• 负责人: Dr.-Ing. Can Dincer
• 金额: --
• 依托单位: Luxembourg Centre for Systems Biomedicine (LCSB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/421356369?language=en
• 关键词: Multiplexed; point; care; testing; inflammatory

The major aim of this project is the implementation of an electrochemical micro-fluidic multiplexed lab-on-a-chip (LOC) platform for the sensitive and on-site testing of a panel of potential Alzheimer’s disease (AD) biomarkers in human body fluids. In this regard, various biomarkers of neuroinflammatory processes, including neurotransmitters and microRNAs, will be measured and evaluated for their applicability in clinical diagnostics. For this purpose, the developed system will be applied for the analysis of relevant biospecimen of Alzheimer patients, primarily human cerebrospinal fluid (CSF) and peripheral blood.In the clinical diagnostics of Alzheimer’s disease, the most prevalent form of dementia, there is a great and urgent need for novel and complementary biomarkers to monitor pathological processes including neurotransmitter depletion or neuroinflammation. As in many cases clinical findings on the basis of a single biomarker are not sufficient for the appropriate diagnosis and surveillance of the therapy, it is highly desirable to gauge different biomarkers simultaneously along with a rapid, low-cost and reliable system. Thus, this project is dedicated to implement a novel detection strategy for the neurotransmitters as well as a panel of miRNAs associated with neuroinflammation using an electrochemical biosensor platform with multiplexed microfluidics for point-of-care testing (POCT).The neurotransmitters, e.g., substance P, not only function as a neuronal signal transmitter, but also as an inflammatory mediator expressed by both peripheral and central nervous system immune cells. Despite a significant amount of research on the role of neurotransmitters in Alzheimer’s disease, neither the involvement of this multifunctional transmitter in the disease pathology nor its usability as a clinical biomarker have been sufficiently clarified. Hence, this project will be especially useful for clarifying the applicability of neurotransmitters as a biomarker in AD.MicroRNAs, small non-coding RNA molecules, play a key role in the regulation of gene expression. Some miRNAs are expressed disease-specific and can utilized for biomarker analysis. Hence, miRNAs are gaining increasing importance as numerous screening studies aim to identify new potential biomarker candidates for cancer, cardiovascular disease, dementias such as AD and neuroinflammation. In the second part of this project, the clinical validation of various miRNAs as potential biomarker candidates for Alzheimer’s disease will be examined to implement and test a 4-plex miRNA panel for clinical diagnosis.A successful demonstration of the proposed microfluidic POCT device will offer many benefits such as direct and rapid detection of miRNAs without any prior amplification. Such a platform would be a major milestone on neuroinflammation analysis in Alzheimer research and beyond as the principle of measurement could be implemented on many areas of application.

该项目的主要目标是实施电化学微流体多重芯片实验室（LOC）平台，用于对人体体液中一组潜在的阿尔茨海默病（AD）生物标志物进行灵敏的现场测试。在这方面，将测量和评估神经炎症过程的各种生物标志物，包括神经递质和 microRNA，以了解其在临床诊断中的适用性。为此，开发的系统将用于分析阿尔茨海默病患者的相关生物样本，主要是人脑脊液（CSF）和外周血。在阿尔茨海默病（最常见的痴呆症）的临床诊断中，迫切需要新型和补充性生物标志物来监测病理过程，包括神经递质耗竭或 神经炎症。由于在许多情况下，基于单一生物标志物的临床发现不足以进行适当的诊断和治疗监测，因此非常需要同时测量不同的生物标志物以及快速、低成本和可靠的系统。因此，该项目致力于使用电化学生物传感器平台和多重微流体进行即时检测（POCT），对神经递质以及一组与神经炎症相关的 miRNA 实施新颖的检测策略。神经递质，例如 P 物质，不仅充当神经元信号递质，还充当炎症介质 由周围和中枢神经系统免疫细胞表达。尽管对神经递质在阿尔茨海默病中的作用进行了大量研究，但这种多功能递质在疾病病理学中的参与及其作为临床生物标志物的可用性都尚未得到充分阐明。因此，该项目对于阐明神经递质作为 AD 生物标志物的适用性特别有用。MicroRNA，即非编码小 RNA 分子，在基因表达的调节中发挥着关键作用。一些 miRNA 具有疾病特异性表达，可用于生物标志物分析。因此，随着大量筛选研究旨在识别癌症、心血管疾病、AD 等痴呆症和神经炎症的新潜在生物标志物候选物，miRNA 变得越来越重要。在该项目的第二部分中，将检查各种 miRNA 作为阿尔茨海默病潜在生物标志物候选者的临床验证，以实施和测试用于临床诊断的 4 重 miRNA 组。所提出的微流控 POCT 设备的成功演示将带来许多好处，例如直接快速检测 miRNA，无需事先进行任何扩增。这样的平台将成为阿尔茨海默病研究及其他领域神经炎症分析的一个重要里程碑，因为测量原理可以在许多应用领域实施。