{"doi":"10.1002/alz.70194","title":"Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice","abstract":"INTRODUCTION: mouse model exhibits early deficits in mossy fiber long-term potentiation (mf-LTP). METHODS: We administered the β-adrenergic receptor agonist isoproterenol (ISO) in vivo and phosphodiesterase type 4 inhibitor GSK356278 in vitro to assess their impact on mf-LTP and contextual fear memory. Fluorescence lifetime imaging (FLIM)-Förster resonance energy transfer (FRET) microscopy was used to visualize impaired and rescued cyclic adenosine monophosphate (cAMP) signaling in dentate gyrus neurons. RESULTS: ISO prevented mf-LTP impairment at 3-4 mo and improved memory by 7 mo. GSK356278 inhibited mf-LTP deficits in a dose-dependent manner. ISO also reduced hyperphosphorylation of synapsin I and microgliosis. DISCUSSION: These findings suggest that β-AR activation and phosphodiesterase 4 (PDE4) inhibition mitigate oAβ-induced memory deficits, supporting enhanced cAMP signaling as a therapeutic target for early AD. HIGHLIGHTS: Early episodic memory deficits in AD linked to oAβ-induced synaptic dysfunction. Isoproterenol and GSK356278 improve mossy fiber-LTP and fear memory deficits. FLIM-FRET shows treatments restore cAMP signaling in dentate gyrus neurons. Isoproterenol reduces synapsin I hyperphosphorylation and microgliosis. Enhancing cAMP signaling may help mitigate early memory deficits in AD.","journal":"Alzheimer s & Dementia","year":2025,"id":516635,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9679,"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":438241,"name":"Jean‐Pierre Bellier","orcid":"0000-0002-8758-8075","position":1,"is_corresponding":false},{"id":1335779,"name":"Adrienne R. Wells","orcid":"0000-0003-3372-5588","position":2,"is_corresponding":false},{"id":1382445,"name":"Paula Montero LIopis","orcid":null,"position":3,"is_corresponding":false},{"id":50950,"name":"Praju Vikas Anekal","orcid":"0000-0002-9482-964X","position":4,"is_corresponding":false},{"id":313195,"name":"Jason S. Tresback","orcid":null,"position":5,"is_corresponding":false},{"id":457384,"name":"Barbara J. Caldarone","orcid":"0000-0003-3503-3104","position":6,"is_corresponding":false},{"id":620375,"name":"Lei Liu","orcid":"0000-0002-9995-9080","position":7,"is_corresponding":false},{"id":237136,"name":"Shaomin Li","orcid":"0000-0001-9451-2151","position":8,"is_corresponding":false},{"id":240635,"name":"Ulf Dettmer","orcid":"0000-0001-6676-0107","position":9,"is_corresponding":false},{"id":471967,"name":"Nagendran Ramalingam","orcid":"0000-0002-9459-3593","position":10,"is_corresponding":false},{"id":7839,"name":"Dennis J. Selkoe","orcid":"0000-0001-8846-9767","position":11,"is_corresponding":false},{"id":536132,"name":"Shan‐Xue Jin","orcid":null,"position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:48:49.486328Z","pmid":"40302031","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":[]}