Article
The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.
Immunity - 12 Aug 2025
Naguib Sarah, Lopez-Lee Chloe, Torres Eileen Ruth, Lee Se-In, Zhu Jingjie, Zhu Daphne, Ye Pearly, Norman Kendra, Zhao Mingrui, Wong Man Ying, Ambaw Yohannes A, Muñoz-Castañeda Rodrigo, Wang Wei, Patel Tark, Bhagwat Maitreyee, Norinsky Rada, Mok Sue-Ann, Walther Tobias C, Farese Robert V, Luo Wenjie, Sinha Subhash C, Wu Zhuhao, Fan Li, Gong Shiaoching, Gan Li
Abstract excerpt
The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy...
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