{"doi":"10.1126/sciadv.abq7105","title":"Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer’s disease","abstract":"The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer's disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3×Tg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD.","journal":"Science Advances","year":2023,"id":320046,"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":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":1029927,"name":"Dan Liu","orcid":"0000-0001-8078-4674","position":1,"is_corresponding":false},{"id":364461,"name":"Huicong Kang","orcid":"0000-0003-1585-8491","position":2,"is_corresponding":false},{"id":1029928,"name":"Lu Lu","orcid":"0000-0002-7700-1939","position":3,"is_corresponding":false},{"id":1029929,"name":"He‐Zhou Huang","orcid":"0000-0003-3155-2732","position":4,"is_corresponding":false},{"id":1030419,"name":"Wen-Qing Ai","orcid":null,"position":5,"is_corresponding":false},{"id":1029930,"name":"Yang Zhou","orcid":"0000-0002-5317-3947","position":6,"is_corresponding":false},{"id":1029931,"name":"Man‐Fei Deng","orcid":"0000-0003-3274-7160","position":7,"is_corresponding":false},{"id":1029932,"name":"Hao Li","orcid":"0000-0003-3559-8965","position":8,"is_corresponding":false},{"id":1029933,"name":"Zhiqiang Liu","orcid":"0000-0002-8837-0369","position":9,"is_corresponding":false},{"id":1029934,"name":"Wei-Feng Zhang","orcid":"0000-0002-8713-6108","position":10,"is_corresponding":false},{"id":1030420,"name":"Yazhuo Hu","orcid":null,"position":11,"is_corresponding":false},{"id":1030421,"name":"Zhitao Han","orcid":null,"position":12,"is_corresponding":false},{"id":1030422,"name":"Hong‐Hong Zhang","orcid":null,"position":13,"is_corresponding":false},{"id":279079,"name":"Jianjun Jia","orcid":"0000-0002-0747-4132","position":14,"is_corresponding":false},{"id":1029935,"name":"Avijite Kumer Sarkar","orcid":"0000-0002-7646-6566","position":15,"is_corresponding":false},{"id":1029936,"name":"Saldin Sharaydeh","orcid":"0000-0001-7653-9393","position":16,"is_corresponding":false},{"id":427738,"name":"Jie Wang","orcid":"0000-0002-2997-3450","position":17,"is_corresponding":false},{"id":207860,"name":"Heng-Ye Man","orcid":"0000-0002-3530-3066","position":18,"is_corresponding":false},{"id":936109,"name":"Marcel Schilling","orcid":"0000-0002-3453-7792","position":19,"is_corresponding":false},{"id":242548,"name":"Lars Bertram","orcid":"0000-0002-0108-124X","position":20,"is_corresponding":false},{"id":1029937,"name":"Youming Lu","orcid":"0000-0002-2422-5656","position":21,"is_corresponding":false},{"id":297691,"name":"Ziyuan Guo","orcid":"0000-0002-2263-0797","position":22,"is_corresponding":false},{"id":1029938,"name":"Ling‐Qiang Zhu","orcid":"0000-0001-9964-9229","position":23,"is_corresponding":false},{"id":1029926,"name":"Lanting Zhou","orcid":"0000-0003-1427-0485","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T01:07:17.361058Z","pmid":"37083538","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":[]}