{"doi":"10.1016/j.jalz.2012.05.1127","title":"F3‐02‐02: O‐GlcNAcylated tau: A link between impaired glucose metabolism and neurodegeneration in Alzheimer's disease","abstract":null,"journal":"Alzheimer's & Dementia","year":2012,"id":659897,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1361133,"name":"Fei Liu","orcid":"0000-0003-1746-8454","position":1,"is_corresponding":false},{"id":1722579,"name":"Inge Grundke‐Iqbal","orcid":null,"position":2,"is_corresponding":false},{"id":1365484,"name":"Khalid Iqbal","orcid":"0000-0003-3769-5224","position":3,"is_corresponding":false},{"id":956870,"name":"Cheng‐Xin Gong","orcid":"0000-0001-5004-7876","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"F3‐02‐02: O‐GlcNAcylated tau: A link between impaired glucose metabolism and neurodegeneration in Alzheimer's disease","abstract":"Brain glucose metabolism is impaired in Alzheimer disease (AD), and this impairment starts before the onset of clinical symptoms, suggesting a causative role in neurodegeneration, but the exact molecular mechanism is unknown. A sensor of intracellular glucose metabolism is O-GlcNAcylation, a posttranslational modification of nucleocytoplasmic proteins by β-N-acetyl-glucosamine (GlcNAc). O-GlcNAcylation of tau affects its abnormal hyperphosphorylation, which is a key mediator of neurodegeneration in AD. The role of O-GlcNAcylation in converting normal tau into abnormally hyperphosphorylated tau was investigated by in vitro, cell culture and in vivo studies. These posttranslational modifications were also studied in postmortem human brain tissue from control and AD cases. We found that O-GlcNAcylation regulated phosphorylation of tau inversely both in vitro and in vivo. In AD brain, O-GlcNAcylation was decreased, and the decrease correlated to hyperphosphorylation of tau. Abnormally hyperphosphorylated tau isolated from AD brain contained much less O-GlcNAc modification than the non-hyperphosphorylated tau. O-GlcNAc modified and regulated brain insulin signal transduction, which plays an important role in learning and memory. Decreased brain O-GlcNAcylation was found to lead to dysregulation of insulin signaling that contributes to neurodegeneration in AD. In AD, impaired glucose uptake/metabolism probably results in decreased O-GlcNAcylation and consequently hyperphosphorylation of tau, leading to neurofibrillary degeneration. Thus, O-GlcNAcylated Tau could be a link between impaired glucose metabolism and neurodegeneration in AD.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W1985543519","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.05818246,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1552526012012599?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1552526012012599?httpAccept=text/plain","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1016%2Fj.jalz.2012.05.1127","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1016/j.jalz.2012.05.1127","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.jalz.2012.05.1127","host_type":"publisher"},{"url":"https://alz-journals.onlinelibrary.wiley.com/doi/pdf/10.1016/j.jalz.2012.05.1127","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jalz.2012.05.1127","host_type":"journal"}],"fields_of_study":["Glycosylation and Glycoproteins Research","Galectins and Cancer Biology","Pharmacological Effects of Natural Compounds"],"mesh_terms":[],"keywords":["Neurodegeneration","Hyperphosphorylation","Alzheimer's disease","Carbohydrate metabolism","Phosphorylation","Tau protein","Tauopathy","Biology","Metabolism","Intracellular","Endocrinology","Cell biology","Internal medicine","Neuroscience","Chemistry","Medicine","Disease"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T07:53:15.005169Z","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":[]}