{"doi":"10.1101/lm.053536.121","title":"Age-dependent attenuation of spatial memory deficits by the histone acetyltransferase p300/CBP-associated factor (PCAF) in 3xTG Alzheimer's disease mice","abstract":"<jats:p>Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.</jats:p>","journal":"Learning &amp; Memory","year":2022,"id":657329,"datarank":0.491637899297485,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.16205421269705206,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.16205421269705206,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":7,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1715945,"name":"Kristen H. Jardine","orcid":null,"position":1,"is_corresponding":false},{"id":1715946,"name":"Alexa Desimone","orcid":null,"position":2,"is_corresponding":false},{"id":1715948,"name":"Megan Zmetana","orcid":null,"position":3,"is_corresponding":false},{"id":114879,"name":"Sabrina Castellano","orcid":null,"position":4,"is_corresponding":false},{"id":1071602,"name":"Ciro Milite","orcid":"0000-0003-1000-1376","position":5,"is_corresponding":false},{"id":887370,"name":"Gianluca Sbardella","orcid":"0000-0003-0748-1145","position":6,"is_corresponding":false},{"id":1715949,"name":"Boyer D. Winters","orcid":null,"position":7,"is_corresponding":false},{"id":1715944,"name":"Samantha D. Creighton","orcid":"0000-0002-3463-2394","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Age-dependent attenuation of spatial memory deficits by the histone acetyltransferase p300/CBP-associated factor (PCAF) in 3xTG Alzheimer's disease mice","abstract":"<jats:p>Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.</jats:p>","is_dataset_classified":null,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35169045","pmcid":"PMC8852226","openalex_id":"https://openalex.org/W4212790569","authors":[],"funders":[{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"400176","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":5},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.1101/lm.053536.121","host_type":"journal"},{"url":"https://doi.org/10.1101/lm.053536.121","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1101/lm.053536.121","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35169045","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8852226","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8852226","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8852226?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1101/lm.053536.121","host_type":""},{"url":"https://hdl.handle.net/11386/4777946","host_type":""},{"url":"http://learnmem.cshlp.org/content/29/3/71","host_type":""}],"fields_of_study":["Histone Deacetylase Inhibitors Research","Alzheimer's disease research and treatments","Epigenetics and DNA Methylation","0301 basic medicine","03 medical and health sciences","0302 clinical medicine","Acetylation","Alzheimer Disease","Animals","Female","Histone Acetyltransferases","Memory Disorders","Mice","Spatial Memory","p300-CBP Transcription Factors","p300-CBP-Associated Factor"],"mesh_terms":["p300-CBP-Associated Factor","Acetylation","Alzheimer Disease","Animals","Female","Memory Disorders","p300-CBP Transcription Factors","Mice","Histone Acetyltransferases","Spatial Memory"],"keywords":["PCAF","Histone acetyltransferase","Histone Acetyltransferases","Acetyltransferase","Histone","Acetylation","P300-CBP Transcription Factors","Cancer research","Neuroscience","Psychology","Medicine","Chemistry","Biochemistry","Gene","Memory Disorders","p300-CBP-Associated Factor","Brief Communication","Mice","Alzheimer Disease","Animals","Female","Spatial Memory"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T00:41:28.309770Z","pmid":null,"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":[]}