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Synaptic dysfunction may contribute to CI in PwMS but cerebrospinal fluid (CSF) synaptic biomarkers are unexplored in MS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>To assess the role of CSF synaptosomal-associated protein 25 (SNAP-25), \u03b2-synuclein, neurogranin and neurofilament light chain protein (NfL) in patients with early relapsing MS with and without CI.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We measured CSF SNAP-25, \u03b2-synuclein, and neurogranin in 48 untreated PwMS and 50 controls with other neurological diseases (ONDs) and tested their associations with neuropsychological and MRI data.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>CSF synaptic protein levels did not discriminate between MS subjects and patients with ONDs, with only SNAP-25 values being slightly increased in MS (<jats:italic>p<\/jats:italic>\u2009=\u20090.009). CSF synaptic markers were positively correlated with each other and with CSF NfL. Moreover, lower biomarker levels were found to be correlated with longer disease duration and lower brain volumes (especially of the thalamus). Moreover, we found significantly lower CSF SNAP-25 (<jats:italic>p<\/jats:italic>\u2009=\u20090.025), \u03b2-synuclein (<jats:italic>p<\/jats:italic>\u2009=\u20090.044), and neurogranin (<jats:italic>p<\/jats:italic>\u2009=\u20090.007) levels in PwMS with vs. without domain-specific cognitive impairment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Lower CSF synaptic biomarker levels were found in PwMS with longer disease duration and lower brain volumes and may identify PwMS at risk of CI.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-024-12851-x","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T13:59:30Z","timestamp":1734789570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["CSF synaptic biomarkers and cognitive impairment in multiple sclerosis"],"prefix":"10.1007","volume":"272","author":[{"given":"Lorenzo","family":"Barba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Sperandei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Di Sabatino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Abu-Rumeileh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Halbgebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Oeckl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Steinacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Di FIlippo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4273-4267","authenticated-orcid":false,"given":"Markus","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"issue":"3","key":"12851_CR1","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/S1474-4422(14)70250-9","volume":"14","author":"MA Rocca","year":"2015","unstructured":"Rocca MA et al (2015) Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis. 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MDF participated on advisory boards and steering committees for and received speaker or writing honoraria, research support and funding for travelling from Alexion, BMS, Bayer, Biogen Idec, Genzyme, Horizon, Janssen, Merck, Mylan, Novartis, Roche, Siemens Healthineers, Teva, and Viatris. MO received consulting fees from Biogen, Axon, Roche, and Grifols and participated on the Biogen ATLAS trial board, all unrelated to the present study. PO, SH, and MO are co-inventors of a patent application for using beta-synuclein measurement in blood (EP4014048A1, US2022283184A1).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"85"}}