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Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["001133"],"award-info":[{"award-number":["001133"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["819644 BioDisOrder"],"award-info":[{"award-number":["819644 BioDisOrder"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013003","name":"Universit\u00e0 degli Studi di Cagliari","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013003","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease displays clinical heterogeneity, presenting with motor and non-motor symptoms. Heterogeneous phenotypes, named brain-first and body-first, may reflect distinct \u03b1-synuclein pathology starting either in the central nervous system or in the periphery. The immune system plays a prominent role in the central and peripheral pathology, with misfolded \u03b1-synuclein being placed at the intersection between neurodegeneration and inflammation. Here, we characterized the inflammatory profile and immune-phenotype of peripheral blood mononuclear cells (PBMCs) from Parkinson\u2019s disease patients upon stimulation with \u03b1-synuclein monomer or oligomer, and investigated relationships of immune parameters with clinical scores of motor and non-motor symptoms. Freshly isolated PBMCs from 21 Parkinson\u2019s disease patients and 18 healthy subjects were exposed in vitro to \u03b1-synuclein species. Cytokine\/chemokine release was measured in the culture supernatant by Multiplex Elisa. The immune-phenotype was studied by FACS-flow cytometry. Correlation analysis was computed between immune parameters and parkinsonian motor and non-motor scales. We found that Parkinson\u2019s disease patients exhibited a dysregulated PBMC-cytokine profile, which remained unaltered after exposure to \u03b1-synuclein species and correlated with both motor and non-motor severity, with a strong correlation observed with olfactory impairment. Exposure of PBMCs from healthy controls to \u03b1-synuclein monomer\/oligomer increased the cytokine\/chemokine release up to patient\u2019s values. Moreover, the PBMCs immune phenotype differed between patients and controls and revealed a prominent association of the Mos profile with olfactory impairment, and of NK profile with constipation. Results suggest that a deranged PBMC-immune profile may reflect distinct clinical subtypes and would fit with the recent classification of Parkinson\u2019s disease into peripheral-first versus brain-first phenotype.<\/jats:p>","DOI":"10.1007\/s00415-024-12554-3","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T07:02:10Z","timestamp":1720594930000},"page":"5916-5929","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune responses to oligomeric \u03b1-synuclein in Parkinson\u2019s disease peripheral blood mononuclear cells"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9725-0473","authenticated-orcid":false,"given":"Ana Florencia","family":"Vega-Benedetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0938-4242","authenticated-orcid":false,"given":"Clara","family":"Porcedda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3260-1754","authenticated-orcid":false,"given":"Tommaso","family":"Ercoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3644-9809","authenticated-orcid":false,"given":"Giuliana","family":"Fusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5517-8223","authenticated-orcid":false,"given":"Chiara","family":"Burgaletto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-847X","authenticated-orcid":false,"given":"Rita","family":"Pillai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7449-9498","authenticated-orcid":false,"given":"Francesca","family":"Palmas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2040-2716","authenticated-orcid":false,"given":"Anna Flavia","family":"Cantone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6613-603X","authenticated-orcid":false,"given":"Fabrizio","family":"Angius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2982-0665","authenticated-orcid":false,"given":"Paolo","family":"Solla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-9546","authenticated-orcid":false,"given":"Alfonso","family":"De Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-9337","authenticated-orcid":false,"given":"Giuseppina","family":"Cantarella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7667-6088","authenticated-orcid":false,"given":"Cesarina","family":"Giallongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-1043","authenticated-orcid":false,"given":"Valeria","family":"Sogos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-439X","authenticated-orcid":false,"given":"Giovanni","family":"Defazio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3104-9010","authenticated-orcid":false,"given":"Anna R.","family":"Carta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"issue":"Suppl 5","key":"12554_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s00415-008-5006-1","volume":"255","author":"KR Chaudhuri","year":"2008","unstructured":"Chaudhuri KR, Naidu Y (2008) Early Parkinson\u2019s disease and non-motor issues. 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