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• W2624884064 abstract "<b><i>Objective:</i></b> Inflammation is clearly associated with Alzheimer disease (AD). Knockout of <i>Nlrp3</i>, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether <i>Aim2</i> deletion also influences the phenotype of a 5XFAD AD mouse model. <b><i>Methods:</i></b> Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, <i>Aim2-/-</i>, 5XFAD, and <i>Aim2-/-</i>;5XFAD mice. <b><i>Results:</i></b> We found that <i>Aim2</i> knockout mitigates Aβ deposition in the cerebral cortex and hippocampus of 5XFAD mice. The activation of microglial cells is also reduced in <i>Aim2-/-</i>;5XFAD brains compared with 5XFAD brains. However, <i>Aim2</i> knockout does not improve memory and anxiety phenotypes of 5XFAD mice in an open field, cued Y-maze, or Barnes maze. Compared with 5XFAD mice, <i>Il-1</i> expression levels are not reduced in <i>Aim2-/-</i>;5XFAD mice. Unexpectedly, <i>Il-6</i> and <i>Il-18</i> expression levels in 5XFAD brains were further increased when <i>Aim2</i> was deleted. Thus, inflammatory cytokine expression in 5XFAD brains is upregulated by <i>Aim2 </i>deletion through an unknown mechanism. <b><i>Conclusion:</i></b> Although <i>Aim2</i> knockout mitigates Aβ deposition and microglial activation, <i>Aim2</i> deletion does not have a beneficial effect on the spatial memory or cytokine expression of 5XFAD mice. Our findings suggest that Aβ aggregation and microglial activation may not always be correlated with the expression of inflammatory cytokines or cognitive function of 5XFAD mice. Our study also implies that different inflammasomes likely perform distinct roles in different physiological and/or pathological events." @default.
• W2624884064 created "2017-06-23" @default.
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• W2624884064 date "2017-01-01" @default.
• W2624884064 modified "2023-09-25" @default.
• W2624884064 title "Deletion of the Inflammasome Sensor <b><i>Aim2</i></b> Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model" @default.
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• W2624884064 doi "https://doi.org/10.1159/000477092" @default.
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