{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:32:41Z","timestamp":1791952361585,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PE2013\u201002359574"],"award-info":[{"award-number":["PE2013\u201002359574"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Locus coeruleus (LC) is one of the earliest structures altered in Alzheimer's disease (AD). Inflammation is also now considered critical in AD pathology, early stage included. However, no association between LC degeneration and the peripheral inflammation has been reported yet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A cohort of 102 patients was studied for which both magnetic resonance imaging (MRI) scans and blood samples were available. LC integrity was assessed by MRI, and plasma soluble TAMs (Tyro3, Axl, and MerTK)\u00a0receptor levels were measured by enzyme\u2010linked immunosorbent assay (ELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We found that plasma levels of the soluble TAMs receptor Axl were correlated with LC rostral degeneration in the whole cohort (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.007), as well as in the AD+ group (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.017), but not in the\u00a0AD\u2013 group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results uncover a new relationship between peripheric markers of inflammation and central early AD neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>In Alzheimer's disease, no link between locus coeruleus\u00a0degeneration and microglial activation was reported.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma Axl, Tyro3, and MerTK\u00a0levels and locus coeruleus integrity were assessed in Alzheimer's disease patients.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Locus coeruleus integrity positively correlates with plasma AXL, linked to microglia activation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Axl\u2013noradrenergic signaling interplay deserves further larger longitudinal studies.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70434","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T23:49:03Z","timestamp":1751413743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Locus coeruleus integrity correlates with plasma soluble Axl levels in Alzheimer's disease patients"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1894-4128","authenticated-orcid":false,"given":"Alessandro","family":"Galgani","sequence":"first","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6597-766X","authenticated-orcid":false,"given":"Arnaud","family":"Mary","sequence":"additional","affiliation":[{"name":"Luxembourg Centre for Systems Biomedicine University of Luxembourg  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione Toscana \u201cG. Monasterio\u201d  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-0163","authenticated-orcid":false,"given":"Nicola","family":"Martini","sequence":"additional","affiliation":[{"name":"Department of Radiology, Fondazione Toscana \u201cG. Monasterio\u201d  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0630-1891","authenticated-orcid":false,"given":"Marco","family":"Scotto","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"},{"name":"Istituto Italiano di Tecnologia  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Tognoni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6142-2384","authenticated-orcid":false,"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-9406","authenticated-orcid":false,"given":"Roberto","family":"Ceravolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2940-8128","authenticated-orcid":false,"given":"Filippo S.","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies University of Pisa  Pisa Italy"},{"name":"I.R.C.C.S. 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