Knockout of the CatB gene, but not BACE1, in AβPPWT/Lon mice results in changes in Aβ-related biomarkers. Brain Aβ40 and Aβ42 (Aβ1–40 and Aβ1–42, respectively) levels were determined by ELISA. The AβPPWT/Lon (control), AβPPWT/Lon × CatB KO (CatB KO), and AβPPWT/Lon × BACE1 KO (BACE1 KO) mice had mean brain Aβ40 levels of 54.6, 9.6, and 59.8 nM, respectively (A), and mean Aβ42 levels of 7.5, 1.5, and 8.4 nM, respectively (B). Brain AβPP-derived CTFβ, generated by β-secretase, was assessed by western blot analysis (C, D). Relative quantitation by densitometry showed that the CatB KO and BACE1 KO mice had mean brain CTFβ levels of 50% and 106% compared to control AβPPWT/Lon mice (100%), respectively (D). AβPP-derived sAβPPα was evaluated by western blot analysis (E, F). Quantitation by densitometry showed that the AβPPWT/Lon, AβPPWT/Lon × CatB KO, AβPPWT/Lon × BACE1 KO mice had mean brain sAβPPα levels of 100%, 150%, and 99% of control AβPPWT/Lon mice, respectively (F). (n = 10 per group, values are expressed as x ± s.e.m., ***statistically significant with p < 0.05).