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

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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.