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NKUA","award":["\u03a42\u0395\u0394\u039a-02813"],"award-info":[{"award-number":["\u03a42\u0395\u0394\u039a-02813"]}]},{"name":"Special Account for Research Grants of NKUA","award":["8638"],"award-info":[{"award-number":["8638"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Even though it is currently well-established that \u03b1-synuclein aggregation is closely associated with the pathological events in Parkinson\u2019s disease (PD) and several other neurodegenerative disorders, collectively called synucleinopathies, the mechanistic link between \u03b1-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 \u03b1-synuclein has been proposed as a potential biomarker in PD, but most of the studies do not discriminate between distinct \u03b1-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 \u03b1-synuclein without cross-reacting with monomers. We have used this assay to determine the levels of aggregated \u03b1-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 \u03b1-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.<\/jats:p>","DOI":"10.3390\/diagnostics13132192","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:33:07Z","timestamp":1687912387000},"page":"2192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Assessment of Aggregated and Exosome-Associated \u03b1-Synuclein in Brain Tissue and Cerebrospinal Fluid Using Specific Immunoassays"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4988-716X","authenticated-orcid":false,"given":"Dimitrios","family":"Anagnostou","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garifalia","family":"Sfakianaki","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Melachroinou","sequence":"additional","affiliation":[{"name":"Center for Basic Research, Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miltiadis","family":"Soutos","sequence":"additional","affiliation":[{"name":"Center for Basic Research, Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-5009","authenticated-orcid":false,"given":"Vassilios","family":"Constantinides","sequence":"additional","affiliation":[{"name":"Neurochemistry Unit, 1st Department of Neurology, Eginition Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-269X","authenticated-orcid":false,"given":"Nishant","family":"Vaikath","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (H.B.K.U.), Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7582-7059","authenticated-orcid":false,"given":"Ioanna","family":"Tsantzali","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology, Attikon General University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-3060","authenticated-orcid":false,"given":"George P.","family":"Paraskevas","sequence":"additional","affiliation":[{"name":"2nd Department of Neurology, Attikon General University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6850-8084","authenticated-orcid":false,"given":"Omar El","family":"Agnaf","sequence":"additional","affiliation":[{"name":"Neurological Disorder Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (H.B.K.U.), Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kostas","family":"Vekrellis","sequence":"additional","affiliation":[{"name":"Center for Basic Research, Biomedical Research Foundation Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3106-8270","authenticated-orcid":false,"given":"Evangelia","family":"Emmanouilidou","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15784 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","first-page":"S53","article-title":"The Synucleinopathies: Twenty Years On","volume":"7","author":"Goedert","year":"2017","journal-title":"J. Parkinsons. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Du, X., Xie, X., and Liu, R. (2020). The Role of \u03b1 -Synuclein Oligomers in Parkinson\u2019s Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228645"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of Brain Pathology Related to Sporadic Parkinson\u2019s Disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. 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Neurodegener."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/alzrt255","article-title":"Levels of Cerebrospinal Fluid \u03b1-Synuclein Oligomers Are Increased in Parkinson\u2019s Disease with Dementia and Dementia with Lewy Bodies Compared to Alzheimer\u2019s Disease","volume":"6","author":"Hansson","year":"2014","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/mds.25772","article-title":"Cerebrospinal Fluid Lysosomal Enzymes and Alpha-Synuclein in Parkinson\u2019s Disease","volume":"29","author":"Parnetti","year":"2014","journal-title":"Mov. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41586-020-2317-6","article-title":"Structures of \u03b1-Synuclein Filaments from Multiple System Atrophy","volume":"585","author":"Schweighauser","year":"2020","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3233\/JPD-160779","article-title":"Implication of Alpha-Synuclein Phosphorylation at S129 in Synucleinopathies: What Have We Learned in the Last Decade?","volume":"6","author":"Oueslati","year":"2016","journal-title":"J. Parkinson\u2019s Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaau4543","DOI":"10.1126\/scisignal.aau4543","article-title":"Manganese Promotes the Aggregation and Prion-like Cell-to-Cell Exosomal Transmission of \u03b1-Synuclein","volume":"12","author":"Harischandra","year":"2019","journal-title":"Sci. Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/brain\/awaa090","article-title":"Microglial Exosomes Facilitate A-Synuclein Transmission in Parkinson\u2019s Disease","volume":"143","author":"Guo","year":"2020","journal-title":"Brain"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/brain\/awv346","article-title":"Induction of \u03b1-Synuclein Aggregate Formation by CSF Exosomes from Patients with Parkinson\u2019s Disease and Dementia with Lewy Bodies","volume":"139","author":"Stuendl","year":"2016","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s40478-017-0445-5","article-title":"Brain-Derived Exosomes from Dementia with Lewy Bodies Propagate \u03b1-Synuclein Pathology","volume":"5","author":"Ngolab","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Vella, L.J., Hill, A.F., and Cheng, L. (2016). Focus on Extracellular Vesicles: Exosomes and Their Role in Protein Trafficking and Biomarker Potential in Alzheimer\u2019s and Parkinson\u2019s Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17020173"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s00401-014-1314-y","article-title":"Plasma Exosomal \u03b1-Synuclein Is Likely CNS-Derived and Increased in Parkinson\u2019s Disease","volume":"128","author":"Shi","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.parkreldis.2019.09.008","article-title":"Neuronal Exosomes in Saliva of Parkinson\u2019s Disease Patients: A Pilot Study","volume":"67","author":"Rani","year":"2019","journal-title":"Park. Relat. Disord."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Taha, H.B., and Ati, S.S. (2023). Evaluation of \u03b1 -Synuclein in CNS-Originating Extracellular Vesicles for Evaluation of \u03b1 -Synuclein in CNS-Originating Extracellular Vesicles for Parkinsonian Disorders: A Systematic Review and Meta-Analysis. Park. Relat. Disord., ahead of print.","DOI":"10.21203\/rs.3.rs-2824641\/v1"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","article-title":"Diagnosis and Management of Dementia with Lewy Bodies: Fourth Consensus Report of the DLB Consortium","volume":"89","author":"McKeith","year":"2017","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS Clinical Diagnostic Criteria for Parkinson\u2019s Disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1212\/01.wnl.0000324625.00404.15","article-title":"Second Consensus Statement on the Diagnosis of Multiple System Atrophy","volume":"71","author":"Gilman","year":"2008","journal-title":"Neurology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical Diagnosis of Progressive Supranuclear Palsy: The Movement Disorder Society Criteria","volume":"32","author":"Respondek","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0896-6273(02)00682-7","article-title":"Neuronal-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human-Synuclein","volume":"34","author":"Giasson","year":"2002","journal-title":"Neuron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/brain\/awv403","article-title":"GABA Transmission via ATP-Dependent K+ Channels Regulates \u03b1-Synuclein Secretion in Mouse Striatum","volume":"139","author":"Emmanouilidou","year":"2016","journal-title":"Brain"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kapaki, E., Paraskevas, G.P., Emmanouilidou, E., and Vekrellis, K. (2013). The Diagnostic Value of CSF \u03b1-Synuclein in the Differential Diagnosis of Dementia with Lewy Bodies vs. Normal Subjects and Patients with Alzheimer\u2019s Disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081654"},{"key":"ref_29","first-page":"1696","article-title":"Modulation of \u03b2-Glucocerebrosidase Increases \u03b1-Synuclein Secretion and Exosome Release in Mouse Models of Parkinson\u2019s Disease","volume":"27","author":"Papadopoulos","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.nbd.2015.04.009","article-title":"Generation and Characterization of Novel Conformation-Specific Monoclonal Antibodies for \u03b1-Synuclein Pathology","volume":"79","author":"Vaikath","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16533","DOI":"10.1038\/s41598-017-15813-8","article-title":"Phosphorylated Exogenous Alpha-Synuclein Fibrils Exacerbate Pathology and Induce Neuronal Dysfunction in Mice","volume":"7","author":"Karampetsou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vaikath, N., Sudhakaran, I., Abdi, I., Gupta, V., Majbour, N., Ghanem, S., Abdesselem, H., Vekrellis, K., and El-Agnaf, O. (2022). Structural and Biophysical Characterization of Stable Alpha-Synuclein Oligomers. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314630"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.parkreldis.2020.03.014","article-title":"Peripheral Alpha-Synuclein Levels in Patients with Genetic and Non-Genetic Forms of Parkinson\u2019s Disease","volume":"73","author":"Emmanouilidou","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00702-019-02137-2","article-title":"High Discriminatory Ability of Peripheral and CFSF Biomarkers in Lewy Body Diseases","volume":"127","author":"Bougea","year":"2020","journal-title":"J. Neural Transm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27290","DOI":"10.1074\/jbc.M114.569814","article-title":"High-Throughput Analysis of Ultrasonication-Forced Amyloid Fibrillation Reveals the Mechanism Underlying the Large Fluctuation in the Lag Time","volume":"289","author":"Umemoto","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Berkhoudt Lassen, L., Gregersen, E., Kathrine Isager, A., Betzer, C., Hahn Kofoed, R., and Henning Jensen, P. (2018). ELISA Method to Detect \u03b1-Synuclein Oligomers in Cell and Animal Models. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196056"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6838","DOI":"10.1523\/JNEUROSCI.5699-09.2010","article-title":"Cell-Produced \u03b1-Synuclein Is Secreted in a Calcium-Dependent Manner by Exosomes and Impacts Neuronal Survival","volume":"30","author":"Emmanouilidou","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/brain\/awac261","article-title":"CSF-Derived Extracellular Vesicles from Patients with Parkinson\u2019s Disease Induce Symptoms and Pathology","volume":"146","author":"Herman","year":"2023","journal-title":"Brain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.expneurol.2010.06.017","article-title":"Elevated Tauopathy and Alpha-Synuclein Pathology in Postmortem Parkinson\u2019s Disease Brains with and without Dementia","volume":"225","author":"Wills","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E2417","DOI":"10.1212\/WNL.0000000000201199","article-title":"Disease-Associated \u03b1-Synuclein Aggregates as Biomarkers of Parkinson Disease Clinical Stage","volume":"99","author":"Majbour","year":"2022","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1002\/acn3.338","article-title":"Alpha-Synuclein RT-QuIC in the CSF of Patients with Alpha-Synucleinopathies","volume":"3","author":"Fairfoul","year":"2016","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1001\/jamaneurol.2016.4547","article-title":"Development of a Biochemical Diagnosis of Parkinson Disease by Detection of \u03b1-Synuclein Misfolded Aggregates in Cerebrospinal Fluid","volume":"74","author":"Shahnawaz","year":"2017","journal-title":"JAMA Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40478-018-0508-2","article-title":"Rapid and Ultra-Sensitive Quantitation of Disease-Associated \u03b1-Synuclein Seeds in Brain and Cerebrospinal Fluid by ASyn RT-QuIC","volume":"6","author":"Groveman","year":"2018","journal-title":"Acta Neuropathol. 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