{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:35:38Z","timestamp":1781807738730,"version":"3.54.5"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":88,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000971","name":"Amyotrophic Lateral Sclerosis Association","doi-asserted-by":"publisher","award":["23-SGP-630"],"award-info":[{"award-number":["23-SGP-630"]}],"id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Office of the Assistant Secretary of Defense for Health Affairs"},{"name":"Amyotrophic Lateral Sclerosis Research Program","award":["HT9425-24-1-0247"],"award-info":[{"award-number":["HT9425-24-1-0247"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>AXL, a receptor tyrosine kinase expressed in neurons and glial cells, involved in neuronal survival, myelination, and regulation of immune responses, can undergo shedding due to the activation of metalloproteases in neuroinflammatory conditions. Indeed, CSF and serum levels of soluble AXL (sAXL) have been correlated with neurodegeneration and cognitive decline in Alzheimer\u2019s disease (AD). Based on these observations, we explored whether sAXL is implicated in amyotrophic lateral sclerosis (ALS). sAXL levels were measured in biofluids (CSF and serum) from two biorepositories, totalling 107 ALS patients, 76 healthy controls, 25 AD patients, 22 patients with multiple sclerosis and 51 patients with ALS disease mimicking disorders (i.e. patients that displayed symptoms resembling ALS, in whom eventually ALS was excluded after a thorough clinical examination). Gender and age were considered as covariate in the statistical analyses. Our results provide the first evidence of sAXL alterations in the CSF and serum of ALS patients at diagnosis and demonstrate a significant association between CSF sAXL levels and disease progression, as well as its prognostic value in ALS. While these observations require validation through multicentre studies, they suggest the involvement of the AXL pathway in ALS pathology and pave the way for leveraging CSF sAXL levels as a biomarker to aid ALS disease stratification.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag086","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T16:27:11Z","timestamp":1774888031000},"source":"Crossref","is-referenced-by-count":1,"title":["Increased CSF levels of soluble AXL at diagnosis correlate with poor prognosis in patients affected by amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3848-9529","authenticated-orcid":false,"given":"Mauro G","family":"Spatafora","sequence":"first","affiliation":[{"name":"Cellular and Molecular Neuropharmacology Laboratory, Department of Biology and Biotechnology \u2018L. Spallanzani\u2019, University of Pavia , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Dubin","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute, KU Leuven (University of Leuven) , Leuven ,","place":["Belgium"]},{"name":"Laboratory Medicine, UZ Leuven (University Hospitals Leuven) , Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teuta","family":"Domi","sequence":"additional","affiliation":[{"name":"Experimental Neuropathology Unit, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0080-6699","authenticated-orcid":false,"given":"Raffaella","family":"Lombardi","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit\u2014Motor Neuron Disease Centre, Fondazione IRCCS Istituto Neurologico C. Besta , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Cabras","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Neuropharmacology Laboratory, Department of Biology and Biotechnology \u2018L. Spallanzani\u2019, University of Pavia , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Dalla Bella","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit\u2014Motor Neuron Disease Centre, Fondazione IRCCS Istituto Neurologico C. Besta , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Consonni","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit\u2014Motor Neuron Disease Centre, Fondazione IRCCS Istituto Neurologico C. Besta , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Quattrini","sequence":"additional","affiliation":[{"name":"Experimental Neuropathology Unit, Institute of Experimental Neurology (INSPE), Division of Neuroscience, IRCCS San Raffaele Scientific Institute , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Verri","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Neuropharmacology Laboratory, Department of Biology and Biotechnology \u2018L. Spallanzani\u2019, University of Pavia , Pavia ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-020X","authenticated-orcid":false,"given":"Giuseppe","family":"Lauria","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit\u2014Motor Neuron Disease Centre, Fondazione IRCCS Istituto Neurologico C. Besta , Milano ,","place":["Italy"]},{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-2357","authenticated-orcid":false,"given":"Philip","family":"Van Damme","sequence":"additional","affiliation":[{"name":"Department of Neurology, UZ Leuven (University Hospitals Leuven) , Leuven ,","place":["Belgium"]},{"name":"Laboratory of Neurobiology, Department of Neurosciences, Leuven Brain Institute, KU Leuven (University of Leuven) , Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-9476","authenticated-orcid":false,"given":"Koen","family":"Poesen","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, Leuven Brain Institute, KU Leuven (University of Leuven) , Leuven ,","place":["Belgium"]},{"name":"Laboratory Medicine, UZ Leuven (University Hospitals Leuven) , Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0513-9517","authenticated-orcid":false,"given":"Nilo","family":"Riva","sequence":"additional","affiliation":[{"name":"3rd Neurology Unit\u2014Motor Neuron Disease Centre, Fondazione IRCCS Istituto Neurologico C. 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