{"doi":"10.1126/science.adk7844","title":"<i>Tlr7</i> drives sex differences in age- and Alzheimer’s disease–related demyelination","abstract":"Alzheimer’s disease (AD) and other age-related disorders associated with demyelination exhibit sex differences. In this work, we used single-nuclei transcriptomics to dissect the contributions of sex chromosomes and gonads in demyelination and AD. In a mouse model of demyelination, we identified the roles of sex chromosomes and gonads in modifying microglia and oligodendrocyte responses before and after myelin loss. In an AD-related mouse model expressing APOE4, XY sex chromosomes heightened interferon (IFN) response and tau-induced demyelination. The X-linked gene, Toll-like receptor 7 ( Tlr7 ), regulated sex-specific IFN response to myelin. Deletion of Tlr7 dampened sex differences while protecting against demyelination. Administering TLR7 inhibitor mitigated tau-induced motor impairment and demyelination in male mice, indicating that Tlr7 plays a role in the male-biased type I Interferon IFN response in aging- and AD-related demyelination.","journal":"Science","year":2024,"id":419043,"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":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295941,"name":"Lay Kodama","orcid":"0000-0001-8419-8445","position":1,"is_corresponding":false},{"id":295940,"name":"Li Fan","orcid":"0000-0003-1780-6919","position":2,"is_corresponding":false},{"id":1013277,"name":"Daphne Zhu","orcid":null,"position":3,"is_corresponding":false},{"id":921916,"name":"Jingjie Zhu","orcid":"0000-0001-8169-4873","position":4,"is_corresponding":false},{"id":270692,"name":"Man Ying Wong","orcid":"0000-0002-2165-9328","position":5,"is_corresponding":false},{"id":1015560,"name":"Pearly Ye","orcid":null,"position":6,"is_corresponding":false},{"id":1205124,"name":"Kendra Norman","orcid":null,"position":7,"is_corresponding":false},{"id":1168275,"name":"Nessa Foxe","orcid":null,"position":8,"is_corresponding":false},{"id":1131367,"name":"Laraib Ijaz","orcid":null,"position":9,"is_corresponding":false},{"id":704435,"name":"Fangmin Yu","orcid":null,"position":10,"is_corresponding":false},{"id":1167865,"name":"Hao Chen","orcid":"0000-0002-9179-5720","position":11,"is_corresponding":false},{"id":1014655,"name":"Gillian Carling","orcid":"0000-0002-1504-1716","position":12,"is_corresponding":false},{"id":441932,"name":"Eileen Ruth S. Torres","orcid":"0000-0002-5340-8734","position":13,"is_corresponding":false},{"id":820475,"name":"Rachel D. Kim","orcid":"0000-0001-6361-6206","position":14,"is_corresponding":false},{"id":250335,"name":"Dena B. Dubal","orcid":"0000-0001-7504-4372","position":15,"is_corresponding":false},{"id":29917,"name":"Shane A. Liddelow","orcid":"0000-0002-0840-1437","position":16,"is_corresponding":false},{"id":672244,"name":"Subhash C. Sinha","orcid":"0000-0001-8916-5677","position":17,"is_corresponding":false},{"id":270700,"name":"Wenjie Luo","orcid":"0000-0003-3752-8266","position":18,"is_corresponding":false},{"id":250399,"name":"Li Gan","orcid":"0000-0003-4600-275X","position":19,"is_corresponding":false},{"id":652032,"name":"Chloe Lopez-Lee","orcid":"0000-0002-1013-3005","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T01:57:14.586331Z","pmid":"39607927","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":[]}