{"doi":"10.1101/2022.11.07.515410","title":"Cryo-EM Structures of Amyloid-β Filaments With the Arctic Mutation (E22G) From Human and Mouse Brains","abstract":"ABSTRACT The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer’s disease. Here we report the high-resolution cryo-EM structures of Aβ filaments from the frontal cortex of a previously described case ( AβPParc1 ) with the Arctic mutation. Most filaments consist of two pairs of non-identical protofilaments that comprise residues V12-V40 (human Arctic fold A) and E11-G37 (human Arctic fold B). They have a substructure (residues F20-G37) in common with the folds of type I and type II Aβ42. When compared to the structures of wild-type Aβ42 filaments, there are subtle conformational changes in the human Arctic folds, because of the lack of a side chain at G22, which may strengthen hydrogen bonding between mutant Aβ molecules and promote filament formation. A minority of Aβ42 filaments of type II was also present, as were tau paired helical filaments. In addition, we report the cryo-EM structures of Aβ filaments with the Arctic mutation from mouse knock-in line App NL-G-F . Most filaments are made of two identical mutant protofilaments that extend from D1-G37 (murine Arctic fold). In a minority of filaments, two dimeric folds pack against each other in an anti-parallel fashion. The murine Arctic fold differs from the human Arctic folds, but shares some substructure.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300594,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9338,"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":614841,"name":"Wenjuan Zhang","orcid":"0000-0002-3011-9956","position":1,"is_corresponding":false},{"id":117572,"name":"Alexey G. Murzin","orcid":null,"position":2,"is_corresponding":false},{"id":818301,"name":"Manuel Schweighauser","orcid":"0000-0002-1848-1610","position":3,"is_corresponding":false},{"id":818303,"name":"Melissa Huang","orcid":"0000-0002-0698-6996","position":4,"is_corresponding":false},{"id":818304,"name":"Sofia Lövestam","orcid":"0000-0002-2152-1476","position":5,"is_corresponding":false},{"id":331722,"name":"Sew‐Yeu Peak‐Chew","orcid":"0000-0002-7602-6384","position":6,"is_corresponding":false},{"id":251064,"name":"Takashi Saito","orcid":"0000-0002-9659-9251","position":7,"is_corresponding":false},{"id":251065,"name":"Takaomi C. Saido","orcid":"0000-0003-1970-6903","position":8,"is_corresponding":false},{"id":991143,"name":"Jennifer A. Macdonald","orcid":"0000-0001-8401-8897","position":9,"is_corresponding":false},{"id":991144,"name":"Isabelle Lavenir","orcid":"0000-0001-8616-891X","position":10,"is_corresponding":false},{"id":268832,"name":"Bernardino Ghetti","orcid":"0000-0002-1842-8019","position":11,"is_corresponding":false},{"id":65581,"name":"Caroline Graff","orcid":"0000-0002-9949-2951","position":12,"is_corresponding":false},{"id":991145,"name":"Amit Kumar","orcid":"0000-0001-7669-0712","position":13,"is_corresponding":false},{"id":467163,"name":"Agneta Nordberg","orcid":"0000-0001-7345-5151","position":14,"is_corresponding":false},{"id":71017,"name":"Michel Goedert","orcid":"0000-0002-5214-7886","position":15,"is_corresponding":false},{"id":614851,"name":"Sjors H. W. Scheres","orcid":"0000-0002-0462-6540","position":16,"is_corresponding":false},{"id":818305,"name":"Yang Yang","orcid":"0000-0001-8912-7240","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","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":[]}