{"doi":"10.1038/s42003-021-02047-8","title":"The anesthetic sevoflurane induces tau trafficking from neurons to microglia","abstract":"Accumulation and spread of tau in Alzheimer's disease and other tauopathies occur in a prion-like manner. However, the mechanisms and downstream consequences of tau trafficking remain largely unknown. We hypothesized that tau traffics from neurons to microglia via extracellular vesicles (EVs), leading to IL-6 generation and cognitive impairment. We assessed mice and neurons treated with anesthetics sevoflurane and desflurane, and applied nanobeam-sensor technology, an ultrasensitive method, to measure tau/p-tau amounts. Sevoflurane, but not desflurane, increased tau or p-tau amounts in blood, neuron culture medium, or EVs. Sevoflurane increased p-tau amounts in brain interstitial fluid. Microglia from tau knockout mice took up tau and p-tau when treated with sevoflurane-conditioned neuron culture medium, leading to IL-6 generation. Tau phosphorylation inhibitor lithium and EVs generation inhibitor GW4869 attenuated tau trafficking. GW4869 mitigated sevoflurane-induced cognitive impairment in mice. Thus, tau trafficking could occur from neurons to microglia to generate IL-6, leading to cognitive impairment.","journal":"Communications Biology","year":2021,"id":155757,"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":57,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"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":395038,"name":"Feng Liang","orcid":"0000-0002-2097-4828","position":1,"is_corresponding":false},{"id":399174,"name":"Lining Huang","orcid":"0000-0001-5754-2706","position":2,"is_corresponding":false},{"id":467482,"name":"Fang Fang","orcid":"0000-0002-3310-6456","position":3,"is_corresponding":false},{"id":260404,"name":"Guang Yang","orcid":"0000-0002-5739-9126","position":4,"is_corresponding":false},{"id":226532,"name":"Rudolph E. Tanzi","orcid":"0000-0002-7032-1454","position":5,"is_corresponding":false},{"id":656474,"name":"Yiying Zhang","orcid":"0000-0001-8197-7558","position":6,"is_corresponding":false},{"id":659438,"name":"Qimin Quan","orcid":null,"position":7,"is_corresponding":false},{"id":395041,"name":"Zhongcong Xie","orcid":"0000-0002-0720-1759","position":8,"is_corresponding":false},{"id":395040,"name":"Yuanlin Dong","orcid":"0000-0002-4760-0519","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:44:03.750995Z","pmid":"33980987","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":[]}