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Extracellular vesicle analysis for biomarker identification in cerebral spinal fluid and blood from patients with Parkinson's disease
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Extracellular vesicle analysis for biomarker identification in cerebral spinal fluid and blood from patients with Parkinson's disease
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Journal Article
Extracellular vesicle analysis for biomarker identification in cerebral spinal fluid and blood from patients with Parkinson's disease
2018
Overview
Background: Parkinson's disease is a progressive neurodegeneration that can begin in olfactory and vagal neurons and may spread via misfolded and aggregated alpha-synuclein in extracellular vesicles. The development of disease-modifying medications can be improved by the discovery of early biomarkers of disease and the characterization of the molecular mechanisms of transfer of aggregated proteins between neurons. We are attempting to identify molecular markers of toxic vesicles as candidate biomarkers for disease progression and therapeutic targets. Methods: We have isolated and characterized exosomes from neuronal and glial cells as well as from cerebrospinal fluid and blood. We have used electron and atomic force microscopy to analyse their physical properties, cell-based assays for functional studies and mass spectrometry-based proteomics to characterize their molecular composition. Results: In cell culture systems, pathological conditions such as mitochondrial stress can affect both physical properties and protein composition of exosomes. In particular, stress-induced exosomes appeared to be smaller and more homogeneous in size than those produced by the cells growing in normal conditions. We have identified proteins altered in exosomes from stressed neuronal and glial cells using mass spectrometry-based proteomic profiling. These candidate biomarkers for toxic exosomes are being used for targeted multiple reaction monitoring assays using extracellular vesicles isolated from cerebral spinal fluid and plasma from patients with Parkinson's disease. Summary/Conclusion: Our goal is to identify robust biomarkers for diagnosis of parkinsonian disorders based on isolation of exosomes from patient samples collected at Umeå University Hospital. These biobanks include longitudinal cerebral spinal fluid samples collected from patients during progression of Parkinson's disease and pre-symptomatic blood samples collected many years prior to diagnosis of disease. The fractionation of biofluids based on extracellular vesicle extraction increases the number of detectable proteins and allows the identification of additional candidate biomarkers for neurodegenerative diseases.
Publisher
John Wiley & Sons, Inc
Subject
