{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:59:02Z","timestamp":1791410342701,"version":"4.3.3"},"posted":{"date-parts":[[2026,3,25]]},"group-title":"Neurology","reference-count":95,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Twenty percent of familial amyotrophic lateral sclerosis (fALS) cases are linked to mutations in the Superoxide Dismutase 1 (\n                  <jats:italic>SOD1)<\/jats:italic>\n                  gene and accumulation of misfolded SOD1 aggregates. SOD1 misfolding from the broader ALS population without\n                  <jats:italic>SOD1<\/jats:italic>\n                  mutations is less clear. Here, we report SOD1 seeding activity in antemortem cerebrospinal fluid (CSF) from ALS participants with and without\n                  <jats:italic>SOD1<\/jats:italic>\n                  mutations during ALS progression. Antemortem CSF from controls,\n                  <jats:italic>SOD1-<\/jats:italic>\n                  ALS, and sporadic ALS (sALS) patients was subjected to SOD1 seed amplification real-time quaking induced conversion (RT-QuIC) assays.\n                  <jats:italic>SOD1<\/jats:italic>\n                  -ALS CSF exhibited shorter lag phase and increased ThioflavinT (ThT) fluorescence amplitude compared to healthy controls and those with spinal muscular atrophy. CSF from sALS participants, who had no mutations in\n                  <jats:italic>SOD1<\/jats:italic>\n                  or nine other ALS risk genes, also displayed SOD1 seeding activity, indicating wild-type SOD1 is aggregate-prone in the broader ALS population. Longitudinal CSF data indicated that SOD1 seeding activity correlates with ALS progression via the ALS Functional Rating Scale Revised (ALSFRS-R) slope decline and CSF neurofilament light. Our sALS CSF cohort primarily comprised of participants less than 2 years from symptom onset, suggesting that SOD1 seeding activity is an early biomarker that may enable inclusion in clinical trials. With the FDA-approval of tofersen (Qalsody), a SOD1-lowering antisense oligonucleotide, new SOD1 diagnostic, prognostic and pharmacodynamic biomarkers may enable SOD1-targeting strategies that could benefit the broader ALS population.\n                <\/jats:p>","DOI":"10.64898\/2026.03.20.26348753","type":"posted-content","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:20:17Z","timestamp":1774462817000},"source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal Analysis of Superoxide Dismutase 1 Seeding Activity in Amyotrophic Lateral Sclerosis Cerebrospinal Fluid"],"prefix":"10.64898","author":[{"given":"Mylene A.","family":"Sebogo","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Weissman Hood Institute at Touro University, 1520 23 St. South, Great Falls, Montana, 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macie C.","family":"Frans","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Weissman Hood Institute at Touro University, 1520 23 St. South, Great Falls, Montana, 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helan","family":"Paulose","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Weissman Hood Institute at Touro University, 1520 23 St. South, Great Falls, Montana, 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Weissman Hood Institute at Touro University, 1520 23 St. South, Great Falls, Montana, 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ging-Yuek","family":"Hsiung","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Cashman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy V.","family":"Ly","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University, 660 S. Euclid Ave, Saint Louis, Missouri, 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-4326","authenticated-orcid":false,"given":"Moses J.","family":"Leavens","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Weissman Hood Institute at Touro University, 1520 23 St. South, Great Falls, Montana, 59405, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032710450954000_2026.03.20.26348753v1.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1603471"},{"key":"2026032710450954000_2026.03.20.26348753v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01272-7"},{"key":"2026032710450954000_2026.03.20.26348753v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116496"},{"key":"2026032710450954000_2026.03.20.26348753v1.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"2026032710450954000_2026.03.20.26348753v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01272-7"},{"key":"2026032710450954000_2026.03.20.26348753v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-01006-0"},{"key":"2026032710450954000_2026.03.20.26348753v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature20413"},{"key":"2026032710450954000_2026.03.20.26348753v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.066"},{"key":"2026032710450954000_2026.03.20.26348753v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2025.107124"},{"key":"2026032710450954000_2026.03.20.26348753v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-00537-7"},{"key":"2026032710450954000_2026.03.20.26348753v1.11","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz078"},{"key":"2026032710450954000_2026.03.20.26348753v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34331-4"},{"key":"2026032710450954000_2026.03.20.26348753v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6803"},{"key":"2026032710450954000_2026.03.20.26348753v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.02.019"},{"key":"2026032710450954000_2026.03.20.26348753v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102972"},{"key":"2026032710450954000_2026.03.20.26348753v1.16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126352"},{"key":"2026032710450954000_2026.03.20.26348753v1.17","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071789"},{"key":"2026032710450954000_2026.03.20.26348753v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.020"},{"key":"2026032710450954000_2026.03.20.26348753v1.19","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac165"},{"key":"2026032710450954000_2026.03.20.26348753v1.20","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01421-9"},{"key":"2026032710450954000_2026.03.20.26348753v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31773-z"},{"key":"2026032710450954000_2026.03.20.26348753v1.22","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1688-8"},{"key":"2026032710450954000_2026.03.20.26348753v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2660"},{"key":"2026032710450954000_2026.03.20.26348753v1.24","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0341-5"},{"key":"2026032710450954000_2026.03.20.26348753v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.05.018"},{"key":"2026032710450954000_2026.03.20.26348753v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47326-x"},{"key":"2026032710450954000_2026.03.20.26348753v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202000451"},{"key":"2026032710450954000_2026.03.20.26348753v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4446"},{"key":"2026032710450954000_2026.03.20.26348753v1.29","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2016-313521"},{"key":"2026032710450954000_2026.03.20.26348753v1.30","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12564-1"},{"key":"2026032710450954000_2026.03.20.26348753v1.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406021200"},{"key":"2026032710450954000_2026.03.20.26348753v1.32","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1016\/S0021-9258(19)44055-6","article-title":"On the stability of bovine superoxide dismutase. 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Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis. In: Araki T, editor. Amyotrophic Lateral Sclerosis [Internet]. Brisbane (AU): Exon Publications; 2021 [cited 2023 Dec 18]. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK573423\/. 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