{"doi":"10.1101/2023.03.07.531435","title":"Microglial MHC-I induction with aging and Alzheimer’s is conserved in mouse models and humans","abstract":"Abstract Major Histocompatibility Complex I (MHC-I) CNS cellular localization and function is still being determined after previously being thought to be absent from the brain. MHC-I expression has been reported to increase with brain aging in mouse, rat, and human whole tissue analyses but the cellular localization was undetermined. Neuronal MHC-I is proposed to regulate developmental synapse elimination and tau pathology in Alzheimer’s disease (AD). Here we report that across newly generated and publicly available ribosomal profiling, cell sorting, and single-cell data, microglia are the primary source of classical and non-classical MHC-I in mice and humans. Translating Ribosome Affinity Purification-qPCR analysis of 3-6 and 18-22 month old (m.o.) mice revealed significant age-related microglial induction of MHC-I pathway genes B2m , H2-D1 , H2-K1 , H2-M3 , H2-Q6 , and Tap1 but not in astrocytes and neurons. Across a timecourse (12-23 m.o.), microglial MHC-I gradually increased until 21 m.o. and then accelerated. MHC-I protein was enriched in microglia and increased with aging. Microglial expression, and absence in astrocytes and neurons, of MHC-I binding Leukocyte Immunoglobulin-like (Lilrs) and Paired immunoglobin-like type 2 (Pilrs) receptor families could enable cell-autonomous MHC-I signaling and increased with aging in mice and humans. Increased microglial MHC-I, Lilrs, and Pilrs were observed in multiple AD mouse models and human AD data across methods and studies. MHC-I expression correlated with p16INK4A , suggesting an association with cellular senescence. Conserved induction of MHC-I, Lilrs, and Pilrs with aging and AD opens the possibility of cell-autonomous MHC-I signaling to regulate microglial reactivation with aging and neurodegeneration.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":389978,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"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":809567,"name":"Kevin D. Pham","orcid":null,"position":1,"is_corresponding":false},{"id":365198,"name":"Adeline H. Machalinski","orcid":null,"position":2,"is_corresponding":false},{"id":333906,"name":"Hunter L. Porter","orcid":"0000-0002-2495-2423","position":3,"is_corresponding":false},{"id":808878,"name":"Harris E. Blankenship","orcid":"0000-0001-7570-4895","position":4,"is_corresponding":false},{"id":817845,"name":"Kyla B. Tooley","orcid":"0000-0001-7484-0991","position":5,"is_corresponding":false},{"id":333910,"name":"Michael B. Stout","orcid":"0000-0002-9996-9123","position":6,"is_corresponding":false},{"id":1011779,"name":"Heather C. Rice","orcid":"0000-0002-5818-4338","position":7,"is_corresponding":false},{"id":333909,"name":"Amanda L. Sharpe","orcid":"0000-0003-3971-5946","position":8,"is_corresponding":false},{"id":333911,"name":"Michael J. Beckstead","orcid":"0000-0002-1574-530X","position":9,"is_corresponding":false},{"id":333902,"name":"Ana J. Chucair‐Elliott","orcid":"0000-0002-0172-1876","position":10,"is_corresponding":false},{"id":333903,"name":"Sarah R. Ocañas","orcid":"0000-0003-4281-0303","position":11,"is_corresponding":false},{"id":333912,"name":"Willard M. Freeman","orcid":"0000-0001-7027-999X","position":12,"is_corresponding":false},{"id":1024771,"name":"Collyn M. Kellogg","orcid":null,"position":0,"is_corresponding":true}],"reference_count":125,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:32.854511Z","pmid":"36945372","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":[]}