{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T13:32:59Z","timestamp":1794058379042,"version":"4.8.0"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Biophysics","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sergey Brin Family Foundation"},{"name":"Valour Foundation"},{"name":"Henry M. 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These aggregates are often comprised of amyloid filaments, most of which appear untwisted or have extremely low twist, complicating high-resolution structural determination by cryogenic electron microscopy (cryo-EM). Here, we isolated filaments from the brain tissue of a patient with dementia with Lewy bodies and show infectivity in a cell line system that propagates Lewy aSyn. Then, we determined 2.3\u20132.9 \u00c5 cryo-EM structures of low-twist aSyn filaments from this tissue and from a publicly available Parkinson\u2019s disease dementia dataset. In both structures, the protofilament adopts a fold highly similar to the canonical Lewy fold with conserved cofactor and peptidic densities. Compared to previously resolved high-twist filaments, the low-twist filament is left-handed and flattened along the filament axis, resulting in register shifts of interlayer contacts, while preserving the overall architecture. Our results establish that low-twist filaments, which include over 75% of disease-associated Lewy aSyn amyloids, share a common structural core with high-twist forms and are the predominant aSyn species in samples that engage in templated infection.<\/jats:p>","DOI":"10.64898\/2026.09.16.752119","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:35:23Z","timestamp":1789709723000},"source":"Crossref","is-referenced-by-count":1,"title":["Cryo-EM Structures of Infectious Low-Twist \u03b1-Synuclein Filaments in Lewy Bodies"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-550X","authenticated-orcid":false,"given":"Nicholas L.","family":"Yan","sequence":"first","affiliation":[{"name":"Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA, 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