{"doi":"10.1101/2025.05.13.653829","title":"Cryo-EM evidence for a common factor in Alzheimer’s and other neurodegenerations","abstract":"In the last seven years, cryo-EM maps of neuropathological fibrils from Alzheimer’s disease and other neurodegenerations have been released by various authors 1–44 . The first publication 11 noted an unknown component coordinating with lysine residues in the protein, a finding recapitulated in many succeeding studies. Previous authors have emphasized difficulties in analysing this component 12,20,28,33,43,45 , but current findings, using powerful visualisation software UCSF ChimeraX 46 on all publicly available maps 1–44 , indicate that the issue is tractable. Lysine-coordinating extra densities have common features, including a Y-shaped substructure, suggestive of a molecular factor in common, in neuropathological fibrils from a wide range of neurodegenerations and involving misfolded proteins beta-amyloid 10,35 , alpha-synuclein 27,37,39,41 , prion protein 17 , tau 1,5,7,8,11,12,15,16,19,22–26,29–33,35,43 and transmembrane protein 106B 5,9,18,20,24,28,36,44 . A similar component, albeit in non-lysine environments, was found in neuropathological fibrils involving TAR DNA-binding protein 43 2,3 and TATA-binding protein-associated factor 15 36 . The results suggest the existence of a common molecular factor, a predominantly anionic polymer, linking these diseases and raising the possibility of a unitary basis for Alzheimer’s and other neurodegenerations. Based on evidence here, RNA is a feasible candidate for this putative common factor. Such findings raise the possibility of new diagnostic tests and treatments for these devastating diseases in the future.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":566000,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1469859,"name":"Leslie R. Bridges","orcid":null,"position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","pmid":"40463114","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":[]}