{"doi":"10.1002/alz.13857","title":"A TrkB and TrkC partial agonist restores deficits in synaptic function and promotes activity‐dependent synaptic and microglial transcriptomic changes in a late‐stage Alzheimer's mouse model","abstract":"INTRODUCTION: Tropomyosin related kinase B (TrkB) and C (TrkC) receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid beta (Aβ) toxicity. Upregulating TrkB/C signaling could reduce Alzheimer's disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction. METHODS: ) and wild-type controls. Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA sequencing. RESULTS: mice, BD10-2 treatment improved memory and LTP deficits. This was accompanied by normalized phosphorylation of protein kinase B (Akt), calcium-calmodulin-dependent kinase II (CaMKII), and AMPA-type glutamate receptors containing the subunit GluA1; enhanced activity-dependent recruitment of synaptic proteins; and increased excitatory synapse number. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription. DISCUSSION: /Aβ-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response. HIGHLIGHTS: Small molecule modulation of tropomyosin related kinase B (TrkB) and C (TrkC) restores long-term potentiation (LTP) and behavior in an Alzheimer's disease (AD) model. Modulation of TrkB and TrkC regulates synaptic activity-dependent transcription. TrkB and TrkC receptors are candidate targets for translational therapeutics. Electrophysiology combined with transcriptomics elucidates synaptic restoration. LTP identifies neuron and microglia AD-relevant human-mouse co-expression modules.","journal":"Alzheimer s & Dementia","year":2024,"id":436757,"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":0.9568,"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":1177540,"name":"Tao Yang","orcid":"0000-0002-7698-3440","position":1,"is_corresponding":false},{"id":584507,"name":"Robert R. Butler","orcid":"0000-0003-0200-8682","position":2,"is_corresponding":false},{"id":699037,"name":"Patricia Morán Losada","orcid":"0000-0002-1991-7842","position":3,"is_corresponding":false},{"id":246388,"name":"Paras S. Minhas","orcid":"0000-0002-7741-3327","position":4,"is_corresponding":false},{"id":1177976,"name":"Halle White","orcid":null,"position":5,"is_corresponding":false},{"id":673642,"name":"Kevin Tran","orcid":"0000-0002-8162-4477","position":6,"is_corresponding":false},{"id":1245108,"name":"Harry Liu","orcid":"0000-0003-3055-5528","position":7,"is_corresponding":false},{"id":1177541,"name":"Danielle A. Simmons","orcid":"0000-0002-6122-840X","position":8,"is_corresponding":false},{"id":1177542,"name":"Vanessa F. Langness","orcid":"0000-0003-3140-3008","position":9,"is_corresponding":false},{"id":246389,"name":"Katrin I. Andreasson","orcid":"0000-0001-8391-4155","position":10,"is_corresponding":false},{"id":227500,"name":"Tony Wyss‐Coray","orcid":"0000-0001-5893-0831","position":11,"is_corresponding":false},{"id":279149,"name":"Frank M. Longo","orcid":"0000-0002-9514-7325","position":12,"is_corresponding":false},{"id":617101,"name":"Amira Latif‐Hernandez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":146,"raw_metadata":null,"created_at":"2026-07-19T02:00:16.989773Z","pmid":"38779814","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":[]}