{"doi":"10.1002/alz.14480","title":"The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease","abstract":"INTRODUCTION: Plaques are a hallmark feature of Alzheimer's disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and their antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites. METHODS: Brain tissue from 5XFAD mice and those that are MR1 deficient (MR1 KO), were analyzed for dystrophic neurites, amyloid plaques, and synapses via immunofluorescence, RNA sequencing, enzyme-linked immunosorbent assay, and western blot. RESULTS: In 8-month-old 5XFAD/MR1 KO mice, there was reduced expression of lysosomal-associated membrane protein 1, ubiquitin, and n-terminal amyloid precursor protein in the hippocampus compared to 5XFAD mice (P < 0.05). 5XFAD/MR1 KO mice also had less insoluble amyloid beta 40 (P < 0.001) and higher levels of postsynaptic density protein 95 (P < 0.01) in the hippocampus. DISCUSSION: Our data contribute additional mechanistic insight into the detrimental role of the MR1/MAIT cell axis in AD pathology development. HIGHLIGHTS: 5XFAD mice lacking the innate immune MR1/MAIT (mucosal-associated invariant T) cell axis (5XFAD/MR1 KO) have reduced numbers of dystrophic neurite markers in the hippocampus at 8 months of age. Hippocampal tissue transcriptional analyses showed reduced expression of genes encoding classical dystrophic neurite markers in 5XFAD/MR1 KO mice. 5XFAD/MR1 KO mice had less insoluble amyloid beta 40 and increased levels of the post-synaptic marker, postsynaptic density protein 95, in the hippocampus than did MR1+ 5XFAD mice.","journal":"Alzheimer s & Dementia","year":2025,"id":549942,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"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":1445335,"name":"Samantha Ackley","orcid":null,"position":1,"is_corresponding":false},{"id":1444599,"name":"Jalyn Warren","orcid":"0009-0001-8128-111X","position":2,"is_corresponding":false},{"id":378954,"name":"Raj Priya","orcid":"0000-0002-9272-9207","position":3,"is_corresponding":false},{"id":300846,"name":"Jun Wan","orcid":"0000-0001-9286-6562","position":4,"is_corresponding":false},{"id":632124,"name":"Sheng Liu","orcid":"0000-0002-2923-3356","position":5,"is_corresponding":false},{"id":378955,"name":"Randy R. Brutkiewicz","orcid":"0000-0002-7396-480X","position":6,"is_corresponding":false},{"id":1067990,"name":"Season K. Wyatt‐Johnson","orcid":"0000-0001-8530-7885","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"39777865","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":[]}