{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Naguib S"],"funding":["NIA NIH HHS"],"pubmed_abstract":["The Christchurch mutation (R136S) on the <i>APOE3</i> (<i>E3</i> <sup><i>S/S</i></sup> ) gene is associated with attenuation of tau load and cognitive decline despite the presence of a causal <i>PSEN1</i> mutation and high levels of amyloid beta pathology in the carrier<sup>1</sup>. However, the specific molecular mechanisms enabling the <i>E3</i> <sup><i>S/S</i></sup> mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse <i>ApoE</i> with wild-type human <i>E3</i> or <i>E3</i> <sup><i>S/S</i></sup> on a tauopathy background. The <i>R136S</i> mutation markedly decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in theta and gamma powers. Additionally, the <i>R136S</i> mutation reduced interferon response to tau "],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.04.25.591140"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11071490"],"repository":["biostudies-literature"],"pubmed_title":["&lt;i&gt;APOE3&lt;/i&gt;-&lt;i&gt;R136S&lt;/i&gt; mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition."],"pmcid":["PMC11071490"],"funding_grant_id":["R01 AG072758","F32 AG085960","RF1 AG079557","R01 AG074541","R01 AG079291"],"pubmed_authors":["Lopez-Lee C","Norinsky R","Gong S","Torres ER","Norman K","Wu Z","Zhao M","Bhagwat M","Patel T","Mok SA","Fan L","Wang W","Wong MY","Ambaw YA","Lee SI","Castaneda R","Zhu D","Farese RV","Naguib S","Zhu J","Sinha S","Ye P","Gan L","Luo W","Walther TC"],"additional_accession":[]},"is_claimable":false,"name":"&lt;i&gt;APOE3&lt;/i&gt;-&lt;i&gt;R136S&lt;/i&gt; mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition.","description":"The Christchurch mutation (R136S) on the <i>APOE3</i> (<i>E3</i> <sup><i>S/S</i></sup> ) gene is associated with attenuation of tau load and cognitive decline despite the presence of a causal <i>PSEN1</i> mutation and high levels of amyloid beta pathology in the carrier<sup>1</sup>. However, the specific molecular mechanisms enabling the <i>E3</i> <sup><i>S/S</i></sup> mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse <i>ApoE</i> with wild-type human <i>E3</i> or <i>E3</i> <sup><i>S/S</i></sup> on a tauopathy background. The <i>R136S</i> mutation markedly decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in theta and gamma powers. Additionally, the <i>R136S</i> mutation reduced interferon response to tau ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jan","modification":"2026-05-30T03:11:36.532Z","creation":"2026-05-30T03:06:40.819Z"},"accession":"S-EPMC11071490","cross_references":{"pubmed":["38712164"],"doi":["10.1101/2024.04.25.591140"]}}