{"doi":"10.3390/ijms241814024","title":"Adipocyte-Derived Small Extracellular Vesicles from Patients with Alzheimer Disease Carry miRNAs Predicted to Target the CREB Signaling Pathway in Neurons","abstract":"Alzheimer disease (AD) is characterized by amyloid-β (Aβ) plaques, neurofibrillary tangles, synaptic dysfunction, and progressive dementia. Midlife obesity increases the risk of developing AD. Adipocyte-derived small extracellular vesicles (ad-sEVs) have been implicated as a mechanism in several obesity-related diseases. We hypothesized that ad-sEVs from patients with AD would contain miRNAs predicted to downregulate pathways involved in synaptic plasticity and memory formation. We isolated ad-sEVs from the serum and cerebrospinal fluid (CSF) of patients with AD and controls and compared miRNA expression profiles. We performed weighted gene co-expression network analysis (WGCNA) on differentially expressed miRNAs to identify highly interconnected clusters correlating with clinical traits. The WGCNA identified a module of differentially expressed miRNAs, in both the serum and CSF, that was inversely correlated with the Mini-Mental State Examination scores. Within this module, miRNAs that downregulate CREB signaling in neurons were highly represented. These results demonstrate that miRNAs carried by ad-sEVs in patients with AD may downregulate CREB signaling and provide a potential mechanistic link between midlife obesity and increased risk of AD.","journal":"International Journal of Molecular Sciences","year":2023,"id":348416,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"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":1090672,"name":"Ankush Bansal","orcid":"0000-0002-5491-1243","position":1,"is_corresponding":false},{"id":1090673,"name":"Laura Reck Cechinel","orcid":"0000-0003-0830-2014","position":2,"is_corresponding":false},{"id":368714,"name":"Kayla Authelet","orcid":"0000-0003-3829-6292","position":3,"is_corresponding":false},{"id":1090674,"name":"Madeleine Goldberg","orcid":"0000-0003-4794-5100","position":4,"is_corresponding":false},{"id":434577,"name":"Evan P. Nadler","orcid":"0000-0001-8312-4647","position":5,"is_corresponding":false},{"id":38380,"name":"C. Dirk Keene","orcid":"0000-0002-5291-1469","position":6,"is_corresponding":false},{"id":250243,"name":"Suman Jayadev","orcid":"0000-0003-3164-9665","position":7,"is_corresponding":false},{"id":253912,"name":"Kimiko Domoto‐Reilly","orcid":"0000-0002-7396-1633","position":8,"is_corresponding":false},{"id":667289,"name":"Gail Li","orcid":null,"position":9,"is_corresponding":false},{"id":27610,"name":"Elaine R. Peskind","orcid":"0000-0002-3667-9129","position":10,"is_corresponding":false},{"id":271796,"name":"Kazue Hashimoto‐Torii","orcid":"0000-0003-4001-8259","position":11,"is_corresponding":false},{"id":264614,"name":"Dedra Buchwald","orcid":"0000-0002-9005-0110","position":12,"is_corresponding":false},{"id":311923,"name":"Robert J. Freishtat","orcid":"0000-0002-7411-2342","position":13,"is_corresponding":false},{"id":1090671,"name":"Rachael Batabyal","orcid":"0000-0003-1573-8860","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:12:06.040073Z","pmid":"37762325","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":[]}