{"doi":"10.1016/j.celrep.2021.109720","title":"Proteopathic tau primes and activates interleukin-1β via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway","abstract":"Pathological hyperphosphorylation and aggregation of tau (pTau) and neuroinflammation, driven by interleukin-1β (IL-1β), are the major hallmarks of tauopathies. Here, we show that pTau primes and activates IL-1β. First, RNA-sequence analysis suggests paired-helical filaments (PHFs) from human tauopathy brain primes nuclear factor κB (NF-κB), chemokine, and IL-1β signaling clusters in human primary microglia. Treating microglia with pTau-containing neuronal media, exosomes, or PHFs causes IL-1β activation, which is NLRP3, ASC, and caspase-1 dependent. Suppression of pTau or ASC reduces tau pathology and inflammasome activation in rTg4510 and hTau mice, respectively. Although the deletion of MyD88 prevents both IL-1β expression and activation in the hTau mouse model of tauopathy, ASC deficiency in myeloid cells reduces pTau-induced IL-1β activation and improves cognitive function in hTau mice. Finally, pTau burden co-exists with elevated IL-1β and ASC in autopsy brains of human tauopathies. Together, our results suggest pTau activates IL-1β via MyD88- and NLRP3-ASC-dependent pathways in myeloid cells, including microglia.","journal":"Cell Reports","year":2021,"id":150822,"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":89,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":640942,"name":"Nicole Maphis","orcid":"0000-0003-3833-1027","position":1,"is_corresponding":false},{"id":372021,"name":"Jessica Binder","orcid":"0000-0003-2091-3950","position":2,"is_corresponding":false},{"id":384250,"name":"Devon Chisholm","orcid":null,"position":3,"is_corresponding":false},{"id":641538,"name":"Lea L. Weston","orcid":null,"position":4,"is_corresponding":false},{"id":641539,"name":"Walter Duran","orcid":null,"position":5,"is_corresponding":false},{"id":641540,"name":"Crina Peterson","orcid":null,"position":6,"is_corresponding":false},{"id":254128,"name":"Amber Zimmerman","orcid":"0000-0001-8212-9059","position":7,"is_corresponding":false},{"id":383087,"name":"Michael A. Mandell","orcid":"0000-0002-5773-2806","position":8,"is_corresponding":false},{"id":641541,"name":"Stephen D. Jett","orcid":null,"position":9,"is_corresponding":false},{"id":308296,"name":"Eileen H. Bigio","orcid":"0000-0002-9554-1138","position":10,"is_corresponding":false},{"id":455454,"name":"Changiz Geula","orcid":"0000-0002-9311-3295","position":11,"is_corresponding":false},{"id":254141,"name":"Nikolaos Mellios","orcid":"0000-0002-0310-1144","position":12,"is_corresponding":false},{"id":254138,"name":"Jason P. Weick","orcid":"0000-0003-3135-9860","position":13,"is_corresponding":false},{"id":322532,"name":"Gary A. Rosenberg","orcid":"0000-0001-7426-7064","position":14,"is_corresponding":false},{"id":104390,"name":"Eicke Latz","orcid":"0000-0003-1488-5666","position":15,"is_corresponding":false},{"id":225475,"name":"Michael T. Heneka","orcid":"0000-0003-4996-1630","position":16,"is_corresponding":false},{"id":272052,"name":"Kiran Bhaskar","orcid":"0000-0001-6064-8106","position":17,"is_corresponding":false},{"id":272051,"name":"Shanya Jiang","orcid":"0000-0001-6564-0859","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:43:06.501849Z","pmid":"34551296","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":[]}