{"doi":"10.1101/2022.01.31.478523","title":"Amyloid fibrils in frontotemporal lobar degeneration with TDP-43 inclusions are composed of TMEM106B, rather than TDP-43","abstract":"Abstract FTLD is the third most common neurodegenerative condition, following only Alzheimer’s and Parkinson’s diseases. FTLD typically presents in 45-64-year-olds with behavioral changes or progressive decline of language skills. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions detected by TDP-43 immunoreactivity. Here, we extracted amyloid fibrils from brains of four patients, representing four out of five FTLD-TDP subclasses and determined their near-atomic resolution structures by cryo-EM. Unexpectedly, all amyloid fibrils examined are composed of a 135-residue C-terminal fragment of TMEM106B, a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP. In addition to TMEM106B fibrils, abundant non-fibrillar aggregated TDP-43 is present, as revealed by immunogold labeling. Our observations confirm that FTLD-TDP is an amyloid-involved disease and suggest that amyloid involvement in FTLD-TDP is of protein TMEM106B, rather than of TDP-43.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302884,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"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":259174,"name":"Qin Cao","orcid":"0000-0003-4207-2697","position":1,"is_corresponding":false},{"id":250200,"name":"M.R. Sawaya","orcid":"0000-0003-0874-9043","position":2,"is_corresponding":false},{"id":473676,"name":"Romany Abskharon","orcid":"0000-0003-1350-0189","position":3,"is_corresponding":false},{"id":8816,"name":"P. Ge","orcid":"0000-0002-2661-8226","position":4,"is_corresponding":false},{"id":91821,"name":"Michael DeTure","orcid":"0000-0002-4363-1262","position":5,"is_corresponding":false},{"id":54753,"name":"Dennis W. Dickson","orcid":"0000-0001-7189-7917","position":6,"is_corresponding":false},{"id":373690,"name":"Janine Y. Fu","orcid":"0000-0002-8854-041X","position":7,"is_corresponding":false},{"id":373692,"name":"Rachel R. Ogorzalek Loo","orcid":"0000-0002-0580-2833","position":8,"is_corresponding":false},{"id":256466,"name":"Joseph A. Loo","orcid":"0000-0001-9989-1437","position":9,"is_corresponding":false},{"id":225464,"name":"David Eisenberg","orcid":"0000-0003-2432-5419","position":10,"is_corresponding":false},{"id":805250,"name":"Yi Xiao Jiang","orcid":"0000-0003-1433-4952","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T00:32:20.348385Z","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":[]}