{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:25:49Z","timestamp":1768505149062,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,28]]},"group-title":"Neuroscience","reference-count":61,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>The amyotrophic lateral sclerosis\/parkinsonism-dementia complex (ALS\/PDC) of the island of Guam and the Kii peninsula of Japan is a fatal neurodegenerative disease of unknown cause that is characterised by the presence of abundant filamentous tau inclusions in brains and spinal cords. Here we used electron cryo-microscopy (cryo-EM) to determine the structures of tau filaments from the cerebral cortex of three cases of ALS\/PDC from Guam and eight cases from Kii, as well as from the spinal cord of two of the Guam cases. Tau filaments had the chronic traumatic encephalopathy (CTE) fold, with variable amounts of Type I and Type II filaments. Paired helical tau filaments were also found in two Kii cases. We also identified a novel Type III CTE tau filament, where protofilaments pack against each other in an anti-parallel fashion. ALS\/PDC is the third known tauopathy with CTE-type filaments and abundant tau inclusions in cortical layers II\/III, the others being CTE and subacute sclerosing panencephalitis. Because these tauopathies are believed to have environmental causes, our findings support the hypothesis that ALS\/PDC is caused by exogenous factors.<\/jats:p>\n                <jats:sec id=\"s1\">\n                  <jats:title>SIGNIFICANCE<\/jats:title>\n                  <jats:p>A neurodegenerative disease of unknown cause on the island of Guam and the Kii peninsula of Japan has been widely studied, because patients can suffer from the combined symptoms of motor neuron disease, parkinsonism and dementia. Abnormal filamentous inclusions made of tau protein characterise this amyotrophic lateral sclerosis\/parkinsonism-dementia complex (ALS\/PDC) and their formation closely correlates with neurodegeneration. Here we have used electron cryo-microscopy (cryo-EM) to show that tau filaments from ALS\/PDC are identical to those from chronic traumatic encephalopathy (CTE), a disease caused by repetitive head impacts or blast waves. CTE tau filaments are also found in subacute sclerosing panencephalitis, which is a rare consequence of measles infection. ALS\/PDC may therefore also be caused by environmental factors.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.04.26.538417","type":"posted-content","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T17:00:19Z","timestamp":1682701219000},"source":"Crossref","is-referenced-by-count":6,"title":["Tau Filaments from Amyotrophic Lateral Sclerosis\/Parkinsonism-Dementia Complex (ALS\/PDC) adopt the CTE Fold"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1277-0363","authenticated-orcid":false,"given":"Chao","family":"Qi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert M.","family":"Verheijen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasumasa","family":"Kokubo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1579-7561","authenticated-orcid":false,"given":"Yang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Tetter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey G.","family":"Murzin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asa","family":"Nakahara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Vermulst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryogen","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshifumi","family":"Hirokawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyomitsu","family":"Oyanagi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiyoshi","family":"Kakita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Ryskeldi-Falcon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-6540","authenticated-orcid":false,"given":"Sjors H.W.","family":"Scheres","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7886","authenticated-orcid":false,"given":"Michel","family":"Goedert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023050200300442000_2023.04.26.538417v1.1","unstructured":"H. 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