{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:37:25Z","timestamp":1777937845312,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The understanding of disease pathophysiology is pivotal for tailored treatments. The spatial distribution of brain damage relies on the regional antigen expression and the local balance of susceptibility and protective elements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>As proof-of-concept, we investigated the spatial association between brain damage and gene expression in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4\u2009+\u2009NMOSD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In this multicenter cross-sectional study, 90 AQP4\u2009+\u2009NMOSD patients and 94 age-matched healthy controls underwent a brain magnetic resonance imaging (MRI). We used T2-hyperintense lesion probability maps and white\/gray matter atrophy as proxies of inflammation and neurodegeneration. The association with the expression of 266 candidate genes was obtained with the Multimodal Environment for Neuroimaging and Genomic Analysis platform. A functional-enrichment analysis investigated overrepresented biological processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In AQP4\u2009+\u2009NMOSD, T2-hyperintense lesions were mainly periventricular; atrophy mostly involved the visual pathway. The expression of AQP4 and complement (C4a and C5) was associated with both inflammation and neurodegeneration. Complement activation and regulation\/uptake of the insulin-like growth factor were the most relevant enriched pathways. Nonspecific pathways related to DNA synthesis and repair were associated with brain atrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Quantitative MRI and gene expression atlas identified the key elements of AQP4\u2009+\u2009NMOSD pathophysiology. This analysis could help in understanding the pathophysiology of antibody-mediated autoimmune disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585241307154","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T06:26:37Z","timestamp":1735626397000},"page":"140-158","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Use of brain MRI and gene expression atlases to reconstruct the pathophysiology of autoimmune neurological disorders: The proof-of-concept of NMOSD"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9342-2410","authenticated-orcid":false,"given":"Laura","family":"Cacciaguerra","sequence":"first","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"Storelli","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Pagani","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-0019","authenticated-orcid":false,"given":"Paolo","family":"Preziosa","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharlota","family":"Mesaros","sequence":"additional","affiliation":[{"name":"Neurology Clinic, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6313-4952","authenticated-orcid":false,"given":"Lucia","family":"Moiola","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Radaelli","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovana","family":"Ivanovic","sequence":"additional","affiliation":[{"name":"Neurology Clinic, University Clinical Centre of Serbia, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivera","family":"Tamas","sequence":"additional","affiliation":[{"name":"Neurology Clinic, University Clinical Centre of Serbia, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Drulovic","sequence":"additional","affiliation":[{"name":"Neurology Clinic, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-4320","authenticated-orcid":false,"given":"Maria A","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"bibr1-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050304"},{"key":"bibr2-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf151"},{"key":"bibr3-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70133-3"},{"key":"bibr4-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30078-8"},{"key":"bibr5-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1901747"},{"key":"bibr6-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31817-3"},{"key":"bibr7-13524585241307154","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/13524585211038291","volume":"28","author":"Pittock SJ","year":"2022","journal-title":"Mult Scler J"},{"key":"bibr8-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26626"},{"key":"bibr9-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.3124"},{"key":"bibr10-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.7.964"},{"key":"bibr11-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511431072"},{"key":"bibr12-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1038\/nature11405"},{"key":"bibr13-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148744"},{"key":"bibr14-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729"},{"key":"bibr15-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"bibr16-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.04.034"},{"key":"bibr17-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1040"},{"key":"bibr18-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.07.007"},{"key":"bibr19-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1027"},{"key":"bibr20-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.01.011"},{"key":"bibr21-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1028"},{"key":"bibr22-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369"},{"key":"bibr23-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"bibr24-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1900866"},{"key":"bibr25-13524585241307154","doi-asserted-by":"publisher","DOI":"10.26502\/jbb.2642-91280131"},{"key":"bibr26-13524585241307154","first-page":"608971","volume":"2024","author":"Weber RZ","year":"2024","journal-title":"Biorxiv"},{"key":"bibr27-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012467"},{"key":"bibr28-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.10.012"},{"key":"bibr29-13524585241307154","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201303376"},{"key":"bibr30-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-20-07710.2003"},{"key":"bibr31-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91695-B"},{"key":"bibr32-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2020192664"},{"key":"bibr33-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01499-1"},{"key":"bibr34-13524585241307154","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2022.835503"},{"key":"bibr35-13524585241307154","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50354-5"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585241307154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585241307154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585241307154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:17:10Z","timestamp":1777695430000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585241307154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,31]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1177\/13524585241307154"],"URL":"https:\/\/doi.org\/10.1177\/13524585241307154","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,31]]}}}