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Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays
Even though it is currently well-established that α-synuclein aggregation is closely associated with the pathological events in Parkinson’s disease (PD) and several other neurodegenerative disorders, collectively called synucleinopathies, the mechanistic link between α-synuclein aggregates and the o...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340737/ https://www.ncbi.nlm.nih.gov/pubmed/37443586 http://dx.doi.org/10.3390/diagnostics13132192 |
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author | Anagnostou, Dimitrios Sfakianaki, Garifalia Melachroinou, Katerina Soutos, Miltiadis Constantinides, Vassilios Vaikath, Nishant Tsantzali, Ioanna Paraskevas, George P. Agnaf, Omar El Vekrellis, Kostas Emmanouilidou, Evangelia |
author_facet | Anagnostou, Dimitrios Sfakianaki, Garifalia Melachroinou, Katerina Soutos, Miltiadis Constantinides, Vassilios Vaikath, Nishant Tsantzali, Ioanna Paraskevas, George P. Agnaf, Omar El Vekrellis, Kostas Emmanouilidou, Evangelia |
author_sort | Anagnostou, Dimitrios |
collection | PubMed |
description | Even though it is currently well-established that α-synuclein aggregation is closely associated with the pathological events in Parkinson’s disease (PD) and several other neurodegenerative disorders, collectively called synucleinopathies, the mechanistic link between α-synuclein aggregates and the onset and progression of neurodegeneration in these diseases remain unclear. The process of aggregation initiates from a structurally distorted monomer that gradually oligomerizes to generate a repertoire of fibrillar and oligomeric multimers that deposit within diseased cells in the brain. Total α-synuclein has been proposed as a potential biomarker in PD, but most of the studies do not discriminate between distinct α-synuclein conformers. To correlate protein measurements to disease pathology, we have developed a conformation-specific ELISA method that selectively detects fibrillar and oligomeric forms of α-synuclein without cross-reacting with monomers. We have used this assay to determine the levels of aggregated α-synuclein in human and mouse brain tissue as well as in CSF and CSF-derived exosomes from patients with synucleinopathy and control subjects. Our results verify the ability of the new assay to detect aggregated α-synuclein in complex matrices and support the idea that the levels of these conformers are related to the age of onset in PD patients, while CSF analysis showed that these species exist in low abundance in CSF and CSF-derived exosomes. Future studies will be required to fully assess the diagnostic usefulness of this ELISA in synucleinopathies. |
format | Online Article Text |
id | pubmed-10340737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103407372023-07-14 Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays Anagnostou, Dimitrios Sfakianaki, Garifalia Melachroinou, Katerina Soutos, Miltiadis Constantinides, Vassilios Vaikath, Nishant Tsantzali, Ioanna Paraskevas, George P. Agnaf, Omar El Vekrellis, Kostas Emmanouilidou, Evangelia Diagnostics (Basel) Article Even though it is currently well-established that α-synuclein aggregation is closely associated with the pathological events in Parkinson’s disease (PD) and several other neurodegenerative disorders, collectively called synucleinopathies, the mechanistic link between α-synuclein aggregates and the onset and progression of neurodegeneration in these diseases remain unclear. The process of aggregation initiates from a structurally distorted monomer that gradually oligomerizes to generate a repertoire of fibrillar and oligomeric multimers that deposit within diseased cells in the brain. Total α-synuclein has been proposed as a potential biomarker in PD, but most of the studies do not discriminate between distinct α-synuclein conformers. To correlate protein measurements to disease pathology, we have developed a conformation-specific ELISA method that selectively detects fibrillar and oligomeric forms of α-synuclein without cross-reacting with monomers. We have used this assay to determine the levels of aggregated α-synuclein in human and mouse brain tissue as well as in CSF and CSF-derived exosomes from patients with synucleinopathy and control subjects. Our results verify the ability of the new assay to detect aggregated α-synuclein in complex matrices and support the idea that the levels of these conformers are related to the age of onset in PD patients, while CSF analysis showed that these species exist in low abundance in CSF and CSF-derived exosomes. Future studies will be required to fully assess the diagnostic usefulness of this ELISA in synucleinopathies. MDPI 2023-06-27 /pmc/articles/PMC10340737/ /pubmed/37443586 http://dx.doi.org/10.3390/diagnostics13132192 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Anagnostou, Dimitrios Sfakianaki, Garifalia Melachroinou, Katerina Soutos, Miltiadis Constantinides, Vassilios Vaikath, Nishant Tsantzali, Ioanna Paraskevas, George P. Agnaf, Omar El Vekrellis, Kostas Emmanouilidou, Evangelia Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays |
title | Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays |
title_full | Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays |
title_fullStr | Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays |
title_full_unstemmed | Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays |
title_short | Assessment of Aggregated and Exosome-Associated α-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays |
title_sort | assessment of aggregated and exosome-associated α-synuclein in brain tissue and cerebrospinal fluid using specific immunoassays |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10340737/ https://www.ncbi.nlm.nih.gov/pubmed/37443586 http://dx.doi.org/10.3390/diagnostics13132192 |
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