{"doi":"10.3389/fnagi.2024.1350239","title":"Reduced GLP-1R availability in the caudate nucleus with Alzheimer’s disease","abstract":"The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to the treatment of neurodegenerative conditions, with a particular focus on Alzheimer's disease (AD). However, the mechanism that underlies regulation of GLP-1R availability in the brain with AD remains poorly understood. Here, using whole transcriptome RNA-Seq of the human postmortem caudate nucleus with AD and chronic hydrocephalus (CH) in the elderly, we found that GLP-1R and select mRNAs expressed in glucose dysmetabolism and dyslipidemia were significantly altered. Furthermore, we detected human RNA indicating a deficiency in doublecortin (DCX) levels and the presence of ferroptosis in the caudate nucleus impacted by AD. Using the genome data viewer, we assessed mutability of GLP-1R and 39 other genes by two factors associated with high mutation rates in chromosomes of four species. Surprisingly, we identified that nucleotide sizes of GLP-1R transcript exceptionally differed in all four species of humans, chimpanzees, rats, and mice by up to 6-fold. Taken together, the protein network database analysis suggests that reduced GLP-1R in the aged human brain is associated with glucose dysmetabolism, ferroptosis, and reduced DCX+ neurons, that may contribute to AD.","journal":"Frontiers in Aging Neuroscience","year":2024,"id":444845,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1133693,"name":"Gabrielle Ivey","orcid":null,"position":1,"is_corresponding":false},{"id":289662,"name":"Adam Cunningham","orcid":"0000-0002-9791-7813","position":2,"is_corresponding":false},{"id":1260762,"name":"Gary Coffman","orcid":null,"position":3,"is_corresponding":false},{"id":1260763,"name":"Tyera Pemberton","orcid":null,"position":4,"is_corresponding":false},{"id":1260272,"name":"Chan Lee","orcid":"0000-0003-1654-4398","position":5,"is_corresponding":false},{"id":289111,"name":"Prabir Patra","orcid":"0000-0002-2917-793X","position":6,"is_corresponding":false},{"id":1260764,"name":"James B. Day","orcid":null,"position":7,"is_corresponding":false},{"id":704650,"name":"Peter H.U. Lee","orcid":"0000-0003-3202-857X","position":8,"is_corresponding":false},{"id":773557,"name":"Joon W. Shim","orcid":"0000-0002-5490-684X","position":9,"is_corresponding":false},{"id":1260271,"name":"Emma Barrett","orcid":"0000-0003-0762-5196","position":0,"is_corresponding":true}],"reference_count":134,"raw_metadata":null,"created_at":"2026-07-19T02:01:37.886033Z","pmid":"38915346","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":[]}