{"doi":"10.1172/jci169064","title":"KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss","abstract":"Synaptic plasticity is obstructed by pathogenic tau in the brain, representing a key mechanism that underlies memory loss in Alzheimer's disease (AD) and related tauopathies. Here, we found that reduced levels of the memory-associated protein KIdney/BRAin (KIBRA) in the brain and increased KIBRA protein levels in cerebrospinal fluid are associated with cognitive impairment and pathological tau levels in disease. We next defined a mechanism for plasticity repair in vulnerable neurons using the C-terminus of the KIBRA protein (CT-KIBRA). We showed that CT-KIBRA restored plasticity and memory in transgenic mice expressing pathogenic human tau; however, CT-KIBRA did not alter tau levels or prevent tau-induced synapse loss. Instead, we found that CT-KIBRA stabilized the protein kinase Mζ (PKMζ) to maintain synaptic plasticity and memory despite tau-mediated pathogenesis. Thus, our results distinguished KIBRA both as a biomarker of synapse dysfunction and as the foundation for a synapse repair mechanism to reverse cognitive impairment in tauopathy.","journal":"Journal of Clinical Investigation","year":2024,"id":422446,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"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":1167962,"name":"Kristeen A. Pareja‐Navarro","orcid":null,"position":1,"is_corresponding":false},{"id":1167445,"name":"Lei Yao","orcid":"0000-0002-5780-5809","position":2,"is_corresponding":false},{"id":1167963,"name":"Jackson H. Chen","orcid":null,"position":3,"is_corresponding":false},{"id":618320,"name":"Ivy Tsz-Lo Wong","orcid":"0000-0002-9761-3422","position":4,"is_corresponding":false},{"id":471936,"name":"Rowan Saloner","orcid":"0000-0002-1351-6183","position":5,"is_corresponding":false},{"id":1167446,"name":"Helen Cifuentes","orcid":"0009-0001-4154-6080","position":6,"is_corresponding":false},{"id":351745,"name":"Alissa L. Nana","orcid":"0000-0003-3474-8044","position":7,"is_corresponding":false},{"id":106304,"name":"Samah Shah","orcid":"0000-0003-4688-1248","position":8,"is_corresponding":false},{"id":275681,"name":"Yaqiao Li","orcid":"0000-0002-9043-0375","position":9,"is_corresponding":false},{"id":369833,"name":"David Le","orcid":"0000-0002-6526-335X","position":10,"is_corresponding":false},{"id":260466,"name":"Salvatore Spina","orcid":"0000-0003-3570-9143","position":11,"is_corresponding":false},{"id":109118,"name":"Lea T. Grinberg","orcid":"0000-0002-6809-0618","position":12,"is_corresponding":false},{"id":32591,"name":"William W. Seeley","orcid":"0000-0003-1410-2027","position":13,"is_corresponding":false},{"id":330926,"name":"Joel H. Kramer","orcid":"0000-0002-1206-404X","position":14,"is_corresponding":false},{"id":572753,"name":"Todd Charlton Sacktor","orcid":"0000-0002-8625-8701","position":15,"is_corresponding":false},{"id":106307,"name":"Birgit Schilling","orcid":"0000-0001-9907-2749","position":16,"is_corresponding":false},{"id":250399,"name":"Li Gan","orcid":"0000-0003-4600-275X","position":17,"is_corresponding":false},{"id":329465,"name":"Kaitlin B. Casaletto","orcid":"0000-0001-5000-7604","position":18,"is_corresponding":false},{"id":250398,"name":"Tara E. Tracy","orcid":"0000-0003-3356-4091","position":19,"is_corresponding":false},{"id":776527,"name":"Grant Kauwe","orcid":null,"position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:57:46.393290Z","pmid":"38299587","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":[]}