{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:50Z","timestamp":1785427250191,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,7]]},"group-title":"Biophysics","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"American Heart Association, Career Development Award","award":["847236"],"award-info":[{"award-number":["847236"]}]},{"name":"National Institutes of Health, National Heart, Lung, and Blood Institute, New Innovator Award","award":["DP2-HL163810"],"award-info":[{"award-number":["DP2-HL163810"]}]},{"award":["I-2121-20220331"],"award-info":[{"award-number":["I-2121-20220331"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"UTSW Endowment, Distinguished Researcher Award from President\u2019s Research Council and start-up funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,7]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  ATTR amyloidosis results from the systemic accumulation of wild-type (ATTRwt) or mutant (ATTRv) transthyretin amyloids, leading to multi-organ dysfunction and death. The disease exhibits variable pathology and penetrance, and its relationship with the amyloid structure remains unclear. Patients carrying the neuropathy-associated variants ATTRvI84S and ATTRv-V122\u0394 present polymorphic ATTR fibrils, in contrast to the consistent morphology reported for most ATTR fibrils to date. Here, we aim to elucidate a potential link between neuropathic symptomatology, distinct mutations, and amyloid structural diversity, using cryo-EM. We determined the\n                  <jats:italic>ex-vivo<\/jats:italic>\n                  fibril structures from the variants ATTRv-P24S, ATTRv-A25S, and ATTRv-D38A, whose patients presented variable clinical manifestations, including neuropathy. Our findings revealed that, despite differences in mutations and diverse clinical phenotypes, these variants share a common amyloid core previously identified in ATTRwt and several other cardiac ATTRv. This structural consistency is significant for the development of structure-guided diagnostic tools capable of addressing the diverse spectrum of ATTR amyloidosis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Determines transthyretin amyloid structures of three human ATTRv by cryo-EM<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Determines the structure of three ex-vivo ATTRv fibrils linked to polyneuropathy.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Reveals structural similarities of ATTRv amyloid cores.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Reveals a common fold despite the different mutations and symptomatology.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Contributes to the understanding of transthyretin aggregation in patients with diverse phenotypes<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.05.667944","type":"posted-content","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T14:10:14Z","timestamp":1754575814000},"source":"Crossref","is-referenced-by-count":3,"title":["A Shared Amyloid Architecture in Cardiac Fibrils from Three Neuropathy-Associated ATTR Variants"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-5242","authenticated-orcid":false,"given":"Maria del 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