{"doi":"10.1002/alz.13464","title":"Anesthesia‐induced hippocampal‐cortical hyperactivity and tau hyperphosphorylation impair remote memory retrieval in Alzheimer's disease","abstract":"INTRODUCTION: Anesthesia often exacerbates memory recall difficulties in individuals with Alzheimer's disease (AD), but the underlying mechanisms remain unclear. METHODS: imaging, viral-based circuit tracing, and chemogenetic approaches to investigate anesthesia-induced remote memory impairment in mouse models of presymptomatic AD. RESULTS: Our study identified pyramidal neuron hyperactivity in the anterior cingulate cortex (ACC) as a significant contributor to anesthesia-induced remote memory impairment. This ACC hyperactivation arises from the disinhibition of local inhibitory circuits and increased excitatory inputs from the hippocampal CA1 region. Inhibiting hyperactivity in the CA1-ACC circuit improved memory recall after anesthesia. Moreover, anesthesia led to increased tau phosphorylation in the hippocampus, and inhibiting this hyperphosphorylation prevented ACC hyperactivity and subsequent memory impairment. DISCUSSION: Hippocampal-cortical hyperactivity plays a role in anesthesia-induced remote memory impairment. Targeting tau hyperphosphorylation shows promise as a therapeutic strategy to mitigate anesthesia-induced neural network dysfunction and retrograde amnesia in AD.","journal":"Alzheimer s & Dementia","year":2023,"id":336549,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"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":829521,"name":"Riya Gupta","orcid":"0000-0002-2004-5447","position":1,"is_corresponding":false},{"id":1016743,"name":"Alejandro Martín‐Ávila","orcid":"0000-0003-0343-1685","position":2,"is_corresponding":false},{"id":443287,"name":"Meng Cui","orcid":"0000-0002-8719-0171","position":3,"is_corresponding":false},{"id":395041,"name":"Zhongcong Xie","orcid":"0000-0002-0720-1759","position":4,"is_corresponding":false},{"id":260404,"name":"Guang Yang","orcid":"0000-0002-5739-9126","position":5,"is_corresponding":false},{"id":1067000,"name":"Kai Chen","orcid":"0000-0001-7708-0705","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T01:10:17.243221Z","pmid":"37695022","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":[]}