{"doi":"10.1101/2022.06.21.496949","title":"Structural polymorphism of amyloid fibrils in cardiac transthyretin amyloidosis revealed by cryo-electron microscopy","abstract":"Abstract The deposition of amyloidogenic transthyretin (ATTR) in ATTR amyloidosis leads to an unexplained variety of clinical phenotypes, including cardiomyopathy. In brain amyloid conditions, there is an apparent association between the clinical phenotype and the amyloid fibril structure. Here, we question this phenotype-structure association in cardiac amyloidoses by determining the cryo-electron microscopy structures of fibrils extracted from the hearts of seven ATTR amyloidosis patients. We found that, in contrast to brain fibrils, cardiac ATTR fibrils display a structural polymorphism that is not genotype-specific, can co-exist within the same individual, and is independent of the cardiac phenotype. This polymorphism challenges the current paradigm of “one disease equals one fibril fold” proposed in tauopathies and synucleinopathies, and questions whether a similar structural heterogeneity occurs in other amyloidoses. One-Sentence Summary Unlike brain amyloid fibrils, cardiac ATTR fibrils are polymorphic independent of genotype and even within the same patient.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297718,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":985849,"name":"Shumaila Afrin","orcid":"0000-0002-8671-1617","position":1,"is_corresponding":false},{"id":271021,"name":"Virender Singh","orcid":"0000-0002-6720-8784","position":2,"is_corresponding":false},{"id":985850,"name":"Yasmin Ahmed","orcid":"0000-0002-5115-2085","position":3,"is_corresponding":false},{"id":985851,"name":"Rose Pedretti","orcid":"0000-0001-6354-3588","position":4,"is_corresponding":false},{"id":985852,"name":"María del Carmen Fernández‐Ramírez","orcid":"0000-0002-3265-5242","position":5,"is_corresponding":false},{"id":169912,"name":"Merrill D. Benson","orcid":null,"position":6,"is_corresponding":false},{"id":250200,"name":"M.R. Sawaya","orcid":"0000-0003-0874-9043","position":7,"is_corresponding":false},{"id":935778,"name":"Preeti Singh","orcid":"0000-0003-2508-5613","position":8,"is_corresponding":false},{"id":259174,"name":"Qin Cao","orcid":"0000-0003-4207-2697","position":9,"is_corresponding":false},{"id":250196,"name":"David R. Boyer","orcid":"0000-0002-4487-0230","position":10,"is_corresponding":false},{"id":900186,"name":"Alexander Pope","orcid":null,"position":11,"is_corresponding":false},{"id":985853,"name":"Paweł M. Wydorski","orcid":"0000-0002-6983-421X","position":12,"is_corresponding":false},{"id":783606,"name":"Siddharth Kumar","orcid":"0000-0001-8053-4122","position":13,"is_corresponding":false},{"id":986254,"name":"Farzeen Chhapra","orcid":null,"position":14,"is_corresponding":false},{"id":225464,"name":"David Eisenberg","orcid":"0000-0003-2432-5419","position":15,"is_corresponding":false},{"id":640664,"name":"Lorena Saelices","orcid":"0000-0002-1904-2150","position":16,"is_corresponding":false},{"id":640665,"name":"Binh A. Nguyen","orcid":"0000-0001-7055-8809","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}