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In ALS-PDC brain samples, we detected high titers of tau and A\u03b2 prions, but we did not detect \u03b1-synuclein prions in either cohort. The specific activity of tau and A\u03b2 prions was increased in Guam ALS-PDC compared with sporadic AD. Applying partial least squares regression to all biochemical and prion infectivity measurements, we demonstrated that the ALS-PDC cohort has a unique molecular signature distinguishable from AD. Our findings argue that Guam ALS-PDC is a distinct double-prion disorder featuring both tau and A\u03b2 prions.<\/jats:p>","DOI":"10.1073\/pnas.2220984120","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T13:47:22Z","timestamp":1679579242000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Guam ALS-PDC is a distinct double-prion disorder featuring both tau and A\u03b2 prions"],"prefix":"10.1073","volume":"120","author":[{"given":"Carlo","family":"Condello","sequence":"first","affiliation":[{"name":"Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158"},{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-2366","authenticated-orcid":false,"given":"Jacob I.","family":"Ayers","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158"},{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton L.","family":"Dalgard","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology, and Genetics, Uniformed Services University of the Health Sciences, F. 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