{"doi":"10.1016/j.stem.2025.06.006","title":"TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice","abstract":"Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than DNMT3A-mutant or wild-type microglia. Strikingly, single-cell RNA sequencing (scRNA-seq) revealed that macrophages and patrolling monocytes were increased in brains of mice transplanted with Tet2-mutant marrow in response to chemokine signaling. These studies reveal a TET2-specific protective effect of CH on AD pathogenesis mediated by peripheral myeloid cell infiltration.","journal":"Cell stem cell","year":2025,"id":511324,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1303085,"name":"Trisha K. 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Buttigieg","orcid":"0000-0002-9584-9861","position":11,"is_corresponding":false},{"id":7759,"name":"Chih-Wei Fan","orcid":null,"position":12,"is_corresponding":false},{"id":813468,"name":"Saul Carcamo","orcid":"0000-0002-1510-1045","position":13,"is_corresponding":false},{"id":239630,"name":"Ruoqiong Cao","orcid":"0000-0001-8100-2136","position":14,"is_corresponding":false},{"id":954012,"name":"Daniel E. Kennedy","orcid":"0000-0001-7937-3069","position":15,"is_corresponding":false},{"id":1213440,"name":"Arushana Maknojia","orcid":"0000-0002-4872-5778","position":16,"is_corresponding":false},{"id":1173567,"name":"Apoorva Thatavarty","orcid":"0000-0001-9828-6331","position":17,"is_corresponding":false},{"id":1369254,"name":"J. 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