{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:17:43Z","timestamp":1793337463051,"version":"4.5.0"},"reference-count":42,"publisher":"BMJ","issue":"8","funder":[{"name":"Ulla-Carin Lindquist Foundation"},{"name":"Bertil H\u00e5llsten Foundation"},{"DOI":"10.13039\/100007464","name":"Torsten S\u00f6derbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007464","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vasterbotten County Council","award":["56103-7002829"],"award-info":[{"award-number":["56103-7002829"]}]},{"DOI":"10.13039\/501100008084","name":"Neurof\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["2012.0091, 2014.0305"],"award-info":[{"award-number":["2012.0091, 2014.0305"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","award":["2011-0262, 2012-0305, 2013-0279, 2016-0303"],"award-info":[{"award-number":["2011-0262, 2012-0305, 2013-0279, 2016-0303"]}],"id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006636","name":"Forskningsr\u00e5det om H\u00e4lsa, Arbetsliv och V\u00e4lf\u00e4rd","doi-asserted-by":"publisher","award":["2012-3167, 2017-03100"],"award-info":[{"award-number":["2012-3167, 2017-03100"]}],"id":[{"id":"10.13039\/501100006636","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Kempe Foundation"},{"DOI":"10.13039\/501100004885","name":"Ume\u00e5 Universitet","doi-asserted-by":"publisher","award":["223-2808-12, 223-1881-13, 2.1.12-1605-14,"],"award-info":[{"award-number":["223-2808-12, 223-1881-13, 2.1.12-1605-14,"]}],"id":[{"id":"10.13039\/501100004885","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      A hallmark of amyotrophic lateral sclerosis (ALS) caused by mutations in\n                      <jats:italic>superoxide dismutase-1<\/jats:italic>\n                      (\n                      <jats:italic>SOD1<\/jats:italic>\n                      ) are inclusions containing SOD1 in motor neurons. Here, we searched for SOD1-positive inclusions in 29 patients carrying ALS-linked mutations in six other genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A panel of antibodies that specifically recognise misfolded SOD1 species were used for immunohistochemical investigations of autopsy tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 18 patients with hexanucleotide-repeat-expansions in\n                      <jats:italic>C9orf72<\/jats:italic>\n                      had inclusions of misfolded wild type (WT) SOD1\n                      <jats:sup>WT<\/jats:sup>\n                      in spinal motor neurons. Similar inclusions were occasionally observed in medulla oblongata and in the motor cortex and frontal lobe. Patients with mutations in\n                      <jats:italic>FUS, KIF5A, NEK1, ALSIN<\/jats:italic>\n                      or\n                      <jats:italic>VAPB<\/jats:italic>\n                      , carried similar SOD1\n                      <jats:sup>WT<\/jats:sup>\n                      inclusions. Minute amounts of misSOD1\n                      <jats:sup>WT<\/jats:sup>\n                      inclusions were detected in 2 of 20 patients deceased from non-neurological causes and in 4 of 10 patients with other neurodegenerative diseases. Comparison was made with 17 patients with 9 different\n                      <jats:italic>SOD1<\/jats:italic>\n                      mutations. Morphologically, the inclusions in patients with mutations in\n                      <jats:italic>C9orf72HRE, FUS, KIF5A, NEK1, VAPB<\/jats:italic>\n                      and\n                      <jats:italic>ALSIN<\/jats:italic>\n                      resembled inclusions in patients carrying the wildtype-like\n                      <jats:italic>\n                        SOD1\n                        <jats:sup>D90A<\/jats:sup>\n                      <\/jats:italic>\n                      mutation, whereas patients carrying unstable\n                      <jats:italic>SOD1<\/jats:italic>\n                      mutations (A4V, V5M, D76Y, D83G, D101G, G114A, G127X, L144F) had larger skein-like SOD1-positive inclusions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and relevance<\/jats:title>\n                    <jats:p>\n                      Abundant inclusions containing misfolded SOD1\n                      <jats:sup>WT<\/jats:sup>\n                      are found in spinal and cortical motor neurons in patients carrying mutations in six ALS-causing genes other than\n                      <jats:italic>SOD1<\/jats:italic>\n                      . This suggests that misfolding of SOD1\n                      <jats:sup>WT<\/jats:sup>\n                      can be part of a common downstream event that may be pathogenic. The new anti-SOD1 therapeutics in development may have applications for a broader range of patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2018-319386","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T17:22:12Z","timestamp":1555435332000},"page":"861-869","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Misfolded SOD1 inclusions in patients with mutations in\n                    <i>C9orf72<\/i>\n                    and other ALS\/FTD-associated genes"],"prefix":"10.1136","volume":"90","author":[{"given":"Karin","family":"Forsberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Graffmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente","family":"Pakkenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Marklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Br\u00e4nnstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0094-5429","authenticated-orcid":false,"given":"Peter Munch","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"2020050722344760000_90.8.861.1","first-page":"744","article-title":"Deux Cas d'atrophie musculaire progressive avec l\u00e9sions de la substance grise et des faisceaux ant\u00e9ro-lat\u00e9raux de la moelle \u00e9pini\u00e9re","volume":"2","author":"Charcot","year":"1869","journal-title":"Arch Physiol Neurol Path"},{"key":"2020050722344760000_90.8.861.2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90191-0"},{"key":"2020050722344760000_90.8.861.3","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000261045.57095.56"},{"key":"2020050722344760000_90.8.861.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.150"},{"key":"2020050722344760000_90.8.861.5","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh509"},{"key":"2020050722344760000_90.8.861.6","doi-asserted-by":"crossref","unstructured":"Brenner D , M\u00fcller K , Wieland T , et al . 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