In this issue of the JCI, Shaftel and colleagues (5) used XAT technology to generate IL-1β^XAT transgenic mice and crossbred these mice with APP/PS1 mice, a mouse model used to study AD. Intrahippocampal injection of FIV-Cre at 6 months of age locally activated the IL-1β transgene and increased the levels of IL-1β and glial fibrillary acid protein (GFAP), indicative of astrocytic activation, as well as Iba-1 and MHC class II, indicative of microglial activation. One month later, instead of observing a worsening of AD-like pathogenesis as expected, the authors found that IL-1β overexpression in the APP/PS1+IL-1β mouse resulted in reduced Aβ plaque deposition and lower insoluble Aβ levels in the injected ipsilateral hippocampus compared with the control-injected contralateral hippocampus. Levels of APP and β-secretase, one of the APP-cleaving enzymes responsible for generating Aβ, were unchanged, suggesting that Aβ production was not affected. Instead, IL-1β overexpression led to increased microglial activation and possibly, as the authors hypothesize, clearance of Aβ deposits by microglial phagocytosis. CA, cornu ammonis; DG, dentate gyrus.