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Inheritance is as a rule dominant, but in carriers of the most prevalent mutation, D90A, disease primarily develops in homozygotes. Increasing evidence suggests that prion-like propagation of SOD1 aggregation is the central pathogenic mechanism. Two structurally different strains of aggregates have been found to arise in human SOD1 (hSOD1) transgenic (Tg) mouse models of ALS. Strain A is formed by most mutants including hSOD1\n                    <jats:sup>G85R<\/jats:sup>\n                    and homozygous hSOD1\n                    <jats:sup>WT<\/jats:sup>\n                    Tg mice, whereas homozygous hSOD1\n                    <jats:sup>D90A<\/jats:sup>\n                    Tg mice form a distinct strain B, but also A. Inoculation of strain A and B seed preparations from Tg mice into lumbar spinal cord of adult hSOD1\n                    <jats:sup>G85R<\/jats:sup>\n                    mice induced templated spreading hSOD1 aggregation and premature ALS-like disease. Seeds from an ALS patient carrying the hSOD1\n                    <jats:sup>G127X<\/jats:sup>\n                    truncation mutation likewise transmitted strain A aggregation and disease. In the present study, we investigated whether seeds prepared from spinal ventral horns from six patients homozygous for the hSOD1\n                    <jats:sup>D90A<\/jats:sup>\n                    mutation could transmit aggregation and disease to adult hSOD1\n                    <jats:sup>G85R<\/jats:sup>\n                    Tg mice. Despite the extensive degeneration and loss of motor neurons in the long-lived D90A patients, two of the seeds significantly shortened the survival of the Tg mice, one transmitting A and the other B-pattern hSOD1 aggregation. Nine different preparations from four human controls lacked effects. The results demonstrate that two distinct aggregate strains can arise and propagate in homozygous hSOD1\n                    <jats:sup>D90A<\/jats:sup>\n                    ALS patients, further supporting the hypothesis that prion-like transmission of hSOD1 aggregation is the primary pathogenic mechanism in SOD1-linked ALS.\n                  <\/jats:p>","DOI":"10.1007\/s00401-026-03078-3","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:51:31Z","timestamp":1788270691000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Seeds from ALS patients homozygous for the SOD1 D90A mutation transmit two types of SOD1 aggregation and motor neuron disease"],"prefix":"10.1007","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5819-890X","authenticated-orcid":false,"given":"Caitlin","family":"Henne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7819-3381","authenticated-orcid":false,"given":"Isabelle","family":"Sigfridsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4201-8204","authenticated-orcid":false,"given":"Thomas","family":"Br\u00e4nnstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2911-6026","authenticated-orcid":false,"given":"Karin M. 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The human studies were approved by the Research Ethics Committee at Ume\u00e5 University (dnr 94\u2013135 and dnr 2014\u201317-31\u00a0M).","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"27"}}