{"doi":"10.1101/2023.09.26.559634","title":"Expansion of highly interferon-responsive T cells in early-onset Alzheimer’s disease","abstract":"Abstract INTRODUCTION Altered immune signatures are emerging as a central theme in neurodegenerative disease, yet little is known about immune responses in early-onset Alzheimer’s disease (EOAD). METHODS We examined single-cell RNA-sequencing (scRNA-seq) data from peripheral blood mononuclear cells (PBMCs) and droplet digital (dd)PCR data from CD4 T cells from participants with EOAD and clinically normal controls. RESULTS We analyzed ~182,000 PBMCs by scRNA-seq and discovered increased interferon signaling-associated gene (ISAG) expression and striking expansion of antiviral-like ISAG hi T cells in EOAD. We isolated CD4 T cells from additional EOAD cases and confirmed increased expression of ISAG hi marker genes. Publicly available cerebrospinal fluid leukocyte scRNA-seq data from late-onset mild cognitive impairment and AD also revealed increased expression of interferon-response genes. DISCUSSION ISAG hi T cells, apparently primed for antiviral activity, are expanded in EOAD. Additional research into these cells and the role of heightened peripheral IFN signaling in neurodegeneration is warranted.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400925,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8252,"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":813926,"name":"Caroline Warly Solsberg","orcid":null,"position":1,"is_corresponding":false},{"id":846136,"name":"Taylor P. Johnson","orcid":"0000-0001-5959-5182","position":2,"is_corresponding":false},{"id":250322,"name":"Luke W. Bonham","orcid":"0000-0002-2533-1266","position":3,"is_corresponding":false},{"id":1177617,"name":"Alexis P. Oddi","orcid":"0000-0001-9151-889X","position":4,"is_corresponding":false},{"id":306551,"name":"Ethan G. Geier","orcid":null,"position":5,"is_corresponding":false},{"id":58513,"name":"Bruce L. Miller","orcid":"0000-0002-2152-4220","position":6,"is_corresponding":false},{"id":230947,"name":"Gil D. Rabinovici","orcid":"0000-0002-3626-4265","position":7,"is_corresponding":false},{"id":250333,"name":"Jennifer S. Yokoyama","orcid":"0000-0001-7274-2634","position":8,"is_corresponding":false},{"id":846135,"name":"Daniel W. Sirkis","orcid":"0000-0003-3440-8859","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37823036","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":[]}