IL-1β^XAT B/b animals were crossed with APP/PS1 mice, generating APP/PS1+IL-1β animals heterozygous for all 3 transgenes. Intrahippocampal FIV-Cre injections were performed at 6 months of age in APP/PS1 and APP/PS1+IL-1β animals to control both for the injection and for viral transduction. After 4 weeks, (7 months of age) the ratio of pathologic indices between the ipsilateral (FIV-Cre injected) and contralateral (uninjected) hemispheres within individual animals was determined. (A and B) Histochemical analysis using the 6E10 antibody (A) and Congo red (B; shown inverted) revealed a reduction in amyloid deposition in the injected ipsilateral hippocampi of APP/PS1+IL-1β mice compared with that of the uninjected contralateral hemispheres. Scale bars: 100 μm (A); 200 μm (B). (C) hIL-1β induction caused significant reductions in Congo red plaque area fraction and frequency. (D and E) Furthermore, hIL-1β overexpression mediated significant reductions in both insoluble Aβ40 and Aβ42 peptides (D), but did not significantly alter levels of their soluble forms (E), as assessed by ELISA. For additional data from C–E, see Supplemental Table 1. n = 6–7 per group. Graphs represent mean ± SEM. *P < 0.05.