{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:09:11Z","timestamp":1792066151327,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:00:00Z","timestamp":1768608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004955","name":"Austrian Research Promotion Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004955","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Austrian Society of Neurology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Anti-IgLON5 disease is a rare neurological disease at the intersection of autoimmunity and neurodegeneration. It is characterized by the presence of anti-IgLON5 antibodies and the development of a brainstem-dominant tau pathology. Recent research indicates that the tau pathology may develop in a time-dependent manner. A three-staged neuropathological classification of the disease has been recently suggested, ranging from no or minimal tau (stage 1) to the characteristic brainstem tau pathology (stage 3) as originally described. This study aimed to characterize the evolution of the disease-associated tauopathy more precisely and to further investigate the early neurodegenerative events in anti-IgLON5 disease.<\/jats:p>\n                  <jats:p>We analysed the medullary region of 14 autopsy cases of anti-IgLON5 disease with different severity grades of tau pathology and varying disease durations, from 6 to 180 months, and compared our findings with five cases with progressive supranuclear palsy and 10 neurologically healthy controls by immunohistochemistry. We applied a broad panel of antibodies targeting different pathological tau post-translational modification sites and the nuclear membrane. In addition, we performed a cell culture of rat hippocampal neurons incubated with purified anti-IgLON5 antibodies to validate the results of the autopsy samples.<\/jats:p>\n                  <jats:p>Based on the tau burden in relation to the pathology stage and disease duration, we determined the chronological appearance of the different post-translational modifications of tau. Phosphorylation at serine 422 was identified as one of the first alterations at stage 1 and showed an early neuronal nuclear staining with simultaneous anti-IgLON5 IgG4 deposits on the neuronal surface as observed by double immunolabelling. Nuclear membrane alterations were also evident by Lamin B1 staining. These were significantly more frequent at stage 1 as compared with controls and adopted the form of nuclear invaginations and crenellations. Crenellations of the nuclear membrane also developed in neuronal cell culture after 3 weeks of antibody incubation, supporting the autopsy findings in vitro.<\/jats:p>\n                  <jats:p>The development of cytoplasmic tau pathology occurs at later stages of the disease with a sequence of post-translational modifications, after an initial nuclear pathology. These new findings contribute to a better understanding of the early pathophysiological events in anti-IgLON5 disease and reinforce the concept of a secondary tauopathy related to an immune-mediated mechanism.<\/jats:p>","DOI":"10.1093\/brain\/awag015","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T12:39:09Z","timestamp":1768394349000},"page":"1704-1717","source":"Crossref","is-referenced-by-count":6,"title":["Brainstem pathology in anti-IgLON5 disease: new insights into early events and tau progression"],"prefix":"10.1093","volume":"149","author":[{"given":"Raphael","family":"Reinecke","sequence":"first","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Nitsch","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Faber","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cansu","family":"Elmas","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Gaubinger","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anika","family":"Simonovska Serra","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Endmayr","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inga","family":"Koneczny","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Berger-Sieczkowski","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Vienna, Medical University of Vienna , Vienna 1090 ,","place":["Austria"]},{"name":"Department of Neurology, Medical University of Vienna, Austria , Vienna 1090 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Blaabjerg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital , Odense C DK-5000 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Elena","family":"Erro","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Universitario de Navarra, Health Research Institute of Navarra (IdisNA) , Pamplona 31008 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Barmherzige Br\u00fcder Vienna , Vienna 1020 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Glatzel","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Medical Center Hamburg-Eppendorf , Hamburg 20251 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Heidbreder","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kepler University Hospital Linz , Linz 4021 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"H\u00f6gl","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck 6020 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casper","family":"Jansen","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology Eastern Netherlands , BB Hengelo 7555 ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9272-529X","authenticated-orcid":false,"given":"Jan","family":"Lewerenz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Ulm , Ulm 89081 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University Hospital Innsbruck , Innsbruck 6020 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-5466","authenticated-orcid":false,"given":"Liisa","family":"Myllykangas","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki and HUS Diagnostic Center, Helsinki University Hospital , Helsinki 00014 ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Krogh Petersen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Odense University Hospital , Odense C DK-5000 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schnider","sequence":"additional","affiliation":[{"name":"Clinical Department of Neurology, University Hospital Wiener Neustadt, N\u00d6 Landesgesundheitsagentur \u2013 Danube Private University , Wiener Neustadt 2700 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4259-8824","authenticated-orcid":false,"given":"Ambra","family":"Stefani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck 6020 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten J","family":"Titulaer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus University Medical Center , Rotterdam 3015 GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Yilmazer-Hanke","sequence":"additional","affiliation":[{"name":"Clinical Neuroanatomy, Department of Neurology, University Hospital Ulm , Ulm 89081 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Weis","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Department of Pathology and Molecular Pathology, Kepler University Hospital and Clinical Research Institute for Neuroscience, Johannes Kepler University , Linz 4021 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Sabater","sequence":"additional","affiliation":[{"name":"Neuroimmunology Program, Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona-Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer, Universitat de Barcelona , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carles","family":"Gaig","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Cl\u00ednic , Barcelona 08036 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Gelpi","sequence":"additional","affiliation":[{"name":"Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna , 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