{"doi":"10.1016/j.celrep.2023.113141","title":"Mast cell deficiency improves cognition and enhances disease-associated microglia in 5XFAD mice","abstract":"Emerging evidence suggests that peripheral immune cells contribute to Alzheimer's disease (AD) neuropathogenesis. Among these, mast cells are known for their functions in allergic reactions and neuroinflammation; however, little is known about their role in AD. Here, we crossed 5XFAD mice with mast cell-deficient strains and observed the effects on AD-related neuropathology and cognitive impairment. We found that mast cell depletion improved contextual fear conditioning in 5XFAD mice without affecting cued fear conditioning, anxiety-like behavior, or amyloid burden. Furthermore, mast cell depletion led to an upregulation of transcriptomic signatures for putatively protective disease-associated microglia and resulted in reduced markers indicative of reactive astrocytes. We hypothesize a system of bidirectional communication between dural mast cells and the brain, where mast cells respond to signals from the brain environment by expressing immune-regulatory mediators, impacting cognition and glial cell function. These findings highlight mast cells as potential therapeutic targets for AD.","journal":"Cell Reports","year":2023,"id":332457,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"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":1058626,"name":"Fanny Hérisson","orcid":"0000-0001-9391-7421","position":1,"is_corresponding":false},{"id":1058627,"name":"Hoang Le","orcid":"0000-0001-8427-3230","position":2,"is_corresponding":false},{"id":1059134,"name":"Nader Jaafar","orcid":null,"position":3,"is_corresponding":false},{"id":229080,"name":"Kashish Chetal","orcid":"0000-0001-9314-5759","position":4,"is_corresponding":false},{"id":1058628,"name":"Mary K. Oram","orcid":"0000-0003-4693-2009","position":5,"is_corresponding":false},{"id":1059135,"name":"Kelly L. Flynn","orcid":null,"position":6,"is_corresponding":false},{"id":1059136,"name":"Evan P. Gavrilles","orcid":null,"position":7,"is_corresponding":false},{"id":260528,"name":"Ruslan I. Sadreyev","orcid":"0000-0002-4240-5466","position":8,"is_corresponding":false},{"id":348206,"name":"Felipe L. Schiffino","orcid":"0000-0002-2877-3406","position":9,"is_corresponding":false},{"id":226532,"name":"Rudolph E. Tanzi","orcid":"0000-0002-7032-1454","position":10,"is_corresponding":false},{"id":60914,"name":"Chih‐Chung Lin","orcid":"0000-0002-0335-9540","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:09:30.139849Z","pmid":"37713312","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":[]}