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To better characterize the neuropathological\/molecular correlates of CP in progressive MS and its potential link with other brain inflammatory compartments, such as perivascular spaces and leptomeninges, the levels, composition and phenotype of CP immune infiltration in lateral ventricles of the hippocampus were examined in 40 post\u2010mortem pathologically confirmed MS and 10 healthy donors, using immunochemistry\/immunofluorescence and in\u2010situ sequencing. Significant inflammation was detected in the CP of 21 out of the 40 MS cases (52%). The degree of CP inflammation was found correlated with: number of CP macrophages (R: 0.878, <jats:italic>p =<\/jats:italic> 1.012 x 10<jats:sup>\u201013<\/jats:sup>) and high frequency of innate immune cells expressing the markers MHC\u2010class II, CD163, CD209, CD11c, TREM2 and TSPO; perivascular inflammation (R: 0.509, <jats:italic>p =<\/jats:italic> 7.921 x 10<jats:sup>\u20104<\/jats:sup>), and less with meningeal inflammation (R: 0.365, <jats:italic>p =<\/jats:italic> 0.021); number of active lesions (R: 0.51, p: 3.524 x 10<jats:sup>\u20105<\/jats:sup>). However, it did not significantly correlate with any clinical\/demographic characteristics of the examined population. In\u2010situ sequencing analysis of gene expression in the CP of 3 representative MS cases and 3 controls revealed regulation of inflammatory pathways mainly related to \u2018type 2 immune response\u2019, \u2018defense to infections\u2019, \u2018antigen processing\/presentation\u2019. Analysis of 78 inflammatory molecules in paired post\u2010mortem CSF, the levels of fibrinogen (R: 0.640, <jats:italic>p =<\/jats:italic> 8.752 x 10<jats:sup>\u20106<\/jats:sup>), PDGF\u2010bb (R: 0.470, <jats:italic>p =<\/jats:italic> 0.002), CXCL13 (R: 0.428, <jats:italic>p =<\/jats:italic> 0.006) and IL15 (R: 0.327, <jats:italic>p =<\/jats:italic> 0.040) were correlated with extent of CP inflammation. Elevated fibrinogen and complement deposition were found in CP and in underlying subependymal periventricular areas, according to \u201csurface\u2010in\u201d gradient associated with concomitant prominent microglia activation. CP inflammation, predominantly characterized by innate immunity, represents another key determinant of intrathecal, compartmentalised inflammation persisting in progressive MS, which may be possibly activated by fibrinogen and influence periventricular pathology, even without substantial association with clinical features.<\/jats:p>","DOI":"10.1111\/bpa.13322","type":"journal-article","created":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T20:44:56Z","timestamp":1733085896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-7763","authenticated-orcid":false,"given":"R.","family":"Magliozzi","sequence":"first","affiliation":[{"name":"Neurology Section of Department of Neuroscience, Biomedicine and Movement University of Verona  Verona Italy"},{"name":"Department of Brain Sciences, Faculty of Medicine Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Hametner","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Mastantuono","sequence":"additional","affiliation":[{"name":"Neurology Section of Department of Neuroscience, Biomedicine and Movement University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mensi","sequence":"additional","affiliation":[{"name":"Neurology Section of Department of Neuroscience, Biomedicine and Movement University of Verona  Verona Italy"},{"name":"Department of Computer Science University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Karimian","sequence":"additional","affiliation":[{"name":"Neurology Section of Department of Neuroscience, Biomedicine and Movement University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-3687","authenticated-orcid":false,"given":"L.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences Swansea University  Swansea UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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