{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:10:48Z","timestamp":1791331848428,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alpha\u2010synuclein (\u03b1\u2010Syn) oligomers and fibrils have been shown to augment the aggregation of TAR DNA\u2010binding Protein 43 (TDP\u201043) monomers in\u00a0vitro, supporting the idea that TDP\u201043 proteinopathies such as ALS may be modulated by the presence of toxic forms of \u03b1\u2010Syn. Recently, parkinsonian features were reported in a study of European patients and Lewy bodies have been demonstrated pathologically in a similar series of patients. Based on these and other considerations, we sought to determine whether seed\u2010competent \u03b1\u2010Syn can be identified in spinal fluid of patients with ALS including familial, sporadic, and Guamanian forms of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on the finding that \u03b1\u2010Syn has been found to be a prion\u2010like protein, we have utilized a validated \u03b1\u2010Synuclein seed amplification assay to determine if seed\u2010competent \u03b1\u2010Syn could be detected in the spinal fluid of patients with ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Toxic species of \u03b1\u2010Syn were detected in CSF in 18 of 127 ALS patients, 5 of whom were from Guam. Two out of twenty six samples from patients with C9orf72 variant ALS had positive seed\u2010amplification assays (SAAs). No positive tests were noted in superoxide dismutase type 1 ALS subjects (<jats:italic>n<\/jats:italic>\u2009=\u200914). The SAA was negative in 31 control subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that a sub\u2010group of ALS occurs in which self\u2010replicating \u03b1\u2010Syn is detectable and likely contributes to its pathogenesis. This finding may have implications for the diagnosis and treatment of this disorder.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16206","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T14:01:17Z","timestamp":1706191277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Misfolded <scp>alpha\u2010synuclein<\/scp> in amyotrophic lateral sclerosis: Implications for diagnosis and treatment"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4200-9268","authenticated-orcid":false,"given":"Richard","family":"Smith","sequence":"first","affiliation":[{"name":"Center for Neurologic Study  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Hovren","sequence":"additional","affiliation":[{"name":"Amprion Clinical Laboratory  San Diego California 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