{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:25:44Z","timestamp":1791062744222,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010815","name":"Stiftelsen f\u00f6r Gamla Tj\u00e4narinnor","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010815","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Biomarkers reflecting the complex pathophysiology of genetic frontotemporal dementia (FTD) will be increasingly important with the advent of therapeutic trials aiming to slow or prevent the disease. In this study, we aimed to identify blood biomarker candidates using a multiplex panel of CNS\u2010related proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We cross\u2010sectionally evaluated 67 carriers (21 presymptomatic and 46 symptomatic) of pathogenic FTD\u2010causing mutations in the\n                      <jats:italic>GRN<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930 symptomatic) and\n                      <jats:italic>C9orf72<\/jats:italic>\n                      (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916 symptomatic) genes and 42 matched non\u2010carriers. Clinical severity was estimated using the CDR Dementia Staging Instrument with National Alzheimer Coordinating Centre Frontotemporal Lobar Degeneration component (CDR plus NACC FTLD). A total of 124 CNS\u2010related proteins were measured in plasma using the NUcleic acid Linked Immuno\u2010Sandwich Assay (NULISA) CNS panel. Group\u2010level changes were then investigated using linear and non\u2010linear regression models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In\n                      <jats:italic>GRN\u2010<\/jats:italic>\n                      and\n                      <jats:italic>C9orf72<\/jats:italic>\n                      \u2010FTD, neurofilament light (NfL) was the most clearly altered protein compared with non\u2010carriers (\n                      <jats:italic>GRN:<\/jats:italic>\n                      \u03b2 [95% CI]\u2009=\u20094.0 standard deviations [3.6\u20134.4],\n                      <jats:italic>C9orf72<\/jats:italic>\n                      : \u03b2\u2009=\u20092.8 [2.2\u20133.4]), followed by neurofilament heavy (NfH;\n                      <jats:italic>GRN<\/jats:italic>\n                      : \u03b2\u2009=\u20090.83 [0.39\u20131.3],\n                      <jats:italic>C9orf72<\/jats:italic>\n                      : \u03b2\u2009=\u20091.4 [0.8\u20132.0]). Proteins exclusively altered in\n                      <jats:italic>GRN<\/jats:italic>\n                      \u2010FTD included glial fibrillary acidic protein (GFAp; \u03b2\u2009=\u20090.50 [0.20\u20130.81]) and vascular cell adhesion protein 1 (VCAM1; Standardized \u03b2\u2009=\u2009\u22120.90 [\u22121.4 to \u22120.38]), changing with increasing disease severity. Neuronal pentraxin receptor (NPTXR; \u03b2\u2009=\u2009\u22120.94 [\u22121.5 to \u22120.4]) was selectively reduced in\n                      <jats:italic>C9orf72\u2010<\/jats:italic>\n                      FTD. Nominally changed proteins in\n                      <jats:italic>C9orf72<\/jats:italic>\n                      \u2010FTD included several inflammatory mediators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using this multiplex panel, established markers recapitulated\u00a0previously established trends, while less\u2010studied biomarker candidates were also identified. If validated in independent cohorts, these candidates could broaden the repertoire of blood biomarkers reflecting genetic FTD pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70704","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:59:41Z","timestamp":1783925981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma Proteomic Changes in\n                    <scp>\n                      <i>GRN<\/i>\n                    <\/scp>\n                    and\n                    <scp>\n                      <i>C9orf72<\/i>\n                    <\/scp>\n                    Frontotemporal Dementia"],"prefix":"10.1111","volume":"33","author":[{"given":"Joel","family":"Simr\u00e9n","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Benedet","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Di Molfetta","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Pola","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00fcbra","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Cantoni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"Libri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Rivolta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7691-1957","authenticated-orcid":false,"given":"Roberta","family":"Ghidoni","sequence":"additional","affiliation":[{"name":"Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease Institute of Neurology, UCL  London UK"},{"name":"UK Dementia Research Institute, UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Hong Kong 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