{"doi":"10.1126/science.add1236","title":"ApoE isoform– and microbiota-dependent progression of neurodegeneration in a mouse model of tauopathy","abstract":"Tau-mediated neurodegeneration is a hallmark of Alzheimer's disease. Primary tauopathies are characterized by pathological tau accumulation and neuronal and synaptic loss. Apolipoprotein E (ApoE)-mediated neuroinflammation is involved in the progression of tau-mediated neurodegeneration, and emerging evidence suggests that the gut microbiota regulates neuroinflammation in an APOE genotype-dependent manner. However, evidence of a causal link between the microbiota and tau-mediated neurodegeneration is lacking. In this study, we characterized a genetically engineered mouse model of tauopathy expressing human ApoE isoforms reared under germ-free conditions or after perturbation of their gut microbiota with antibiotics. Both of these manipulations reduced gliosis, tau pathology, and neurodegeneration in a sex- and ApoE isoform-dependent manner. The findings reveal mechanistic and translationally relevant interrelationships between the microbiota, neuroinflammation, and tau-mediated neurodegeneration.","journal":"Science","year":2023,"id":315026,"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":247,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1014820,"name":"David O’Donnell","orcid":"0000-0001-6239-7988","position":1,"is_corresponding":false},{"id":622886,"name":"Nimansha Jain","orcid":"0000-0001-5360-5466","position":2,"is_corresponding":false},{"id":236544,"name":"Jason D. Ulrich","orcid":"0000-0002-4743-926X","position":3,"is_corresponding":false},{"id":615374,"name":"Jasmin Herz","orcid":"0000-0001-6325-863X","position":4,"is_corresponding":false},{"id":678587,"name":"Yuhao Li","orcid":"0000-0003-2413-0937","position":5,"is_corresponding":false},{"id":851575,"name":"Mackenzie Lemieux","orcid":"0000-0001-6015-8668","position":6,"is_corresponding":false},{"id":314947,"name":"Jiye Cheng","orcid":"0000-0002-0266-3997","position":7,"is_corresponding":false},{"id":259735,"name":"Hao Hu","orcid":"0000-0003-3622-9897","position":8,"is_corresponding":false},{"id":236541,"name":"Javier Remolina Serrano","orcid":"0000-0002-5937-0212","position":9,"is_corresponding":false},{"id":319257,"name":"Xin Bao","orcid":null,"position":10,"is_corresponding":false},{"id":1014821,"name":"Emily Franke","orcid":"0000-0002-0887-957X","position":11,"is_corresponding":false},{"id":218482,"name":"Maria Karlsson","orcid":"0000-0002-2463-0598","position":12,"is_corresponding":false},{"id":1014822,"name":"Martin Meier","orcid":"0000-0001-8642-0409","position":13,"is_corresponding":false},{"id":254507,"name":"Su Deng","orcid":"0000-0002-0835-2452","position":14,"is_corresponding":false},{"id":350734,"name":"Chandni Desai","orcid":"0000-0002-3708-3634","position":15,"is_corresponding":false},{"id":868536,"name":"Hemraj B. Dodiya","orcid":"0000-0002-0908-0014","position":16,"is_corresponding":false},{"id":1015649,"name":"Janaki Lelwala‐Guruge","orcid":null,"position":17,"is_corresponding":false},{"id":36382,"name":"Scott A. Handley","orcid":"0000-0002-2143-6570","position":18,"is_corresponding":false},{"id":109378,"name":"Jonathan Kipnis","orcid":"0000-0002-3714-517X","position":19,"is_corresponding":false},{"id":77488,"name":"Sangram S. Sisodia","orcid":"0000-0002-4039-8864","position":20,"is_corresponding":false},{"id":19791,"name":"Jeffrey I. Gordon","orcid":"0000-0001-8304-3548","position":21,"is_corresponding":false},{"id":27592,"name":"David M. Holtzman","orcid":"0000-0002-3400-0856","position":22,"is_corresponding":false},{"id":641104,"name":"Dong-oh Seo","orcid":"0000-0003-0315-4489","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:06:02.898877Z","pmid":"36634180","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":[]}