{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Udeochu JC"],"funding":["Tau Consortium CureAD Fund Daedalus Fund","NICHD NIH HHS","NIA NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute on Aging","CureAD Fund Daedalus Fund","JumpStart Research Career Development Program, Weill Cornell Medicine","BrightFocus Foundation","JPB Foundation","U.S. Department of Health & Human Services | National Institutes of Health","Boston Children’s Hospital"],"pagination":["737-750"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10166855"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(5)"],"pubmed_abstract":["Pathological hallmarks of Alzheimer's disease (AD) precede clinical symptoms by years, indicating a period of cognitive resilience before the onset of dementia. Here, we report that activation of cyclic GMP-AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of Cgas in mice with tauopathy diminished the microglial IFN-I response, preserved synapse integrity and plasticity and protected against cognitive impairment without affecting the pathogenic tau load. cGAS ablation increased, while activation of IFN-I decreased, th"],"journal":["Nature neuroscience"],"pubmed_title":["Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience."],"pmcid":["PMC10166855"],"funding_grant_id":["5K12HD052896","A20201312F","K01 AG057862","R01AG064239","R01AG072758","K12 HD052896","T32 HD098061","R01 AG074541","R01AG054214","R01 AG054214","R01AG074541","R01 AG072758","R01 AG064239"],"pubmed_authors":["Gong S","Corona C","Raju RM","Zhao M","Yarahmady A","Sinha SC","Kauwe G","Fan L","Mok SA","Nagiri RK","Wong MY","Torres ERS","Tracy TE","Udeochu JC","Lo I","Carling GK","McGurran H","Coronas-Samano G","Mousa GA","Gill MT","Huang Y","Ye P","Ratan RR","Gan L","Amin S","Luo W","Liu B","Tsai LH","Holtzman J"],"additional_accession":[]},"is_claimable":false,"name":"Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience.","description":"Pathological hallmarks of Alzheimer's disease (AD) precede clinical symptoms by years, indicating a period of cognitive resilience before the onset of dementia. Here, we report that activation of cyclic GMP-AMP synthase (cGAS) diminishes cognitive resilience by decreasing the neuronal transcriptional network of myocyte enhancer factor 2c (MEF2C) through type I interferon (IFN-I) signaling. Pathogenic tau activates cGAS and IFN-I responses in microglia, in part mediated by cytosolic leakage of mitochondrial DNA. Genetic ablation of Cgas in mice with tauopathy diminished the microglial IFN-I response, preserved synapse integrity and plasticity and protected against cognitive impairment without affecting the pathogenic tau load. cGAS ablation increased, while activation of IFN-I decreased, th","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-05-28T19:51:32.847Z","creation":"2024-11-21T05:38:25.605Z"},"accession":"S-EPMC10166855","cross_references":{"pubmed":["37095396"],"doi":["10.1038/s41593-023-01315-6"]}}