Effects of a combination of BACE1 haploinsufficiency and neprilysin overexpression on β-amyloidogenic processing of APP in 12-month-old 5XFAD mice. (A) Representative immunoblots of protein extracts from hemibrain homogenates of mice. (B–E) Immunoreactive bands were quantified and expressed as the percentage of 5XFAD control mice (n = 3–4 mice per group). Note that BACE1 expression is reduced below wild-type controls in BACE1+/− · NEP · 5XFAD mice, as expected by a single BACE1 allele ablation and the complete abolishment of eIF2α phosphorylation-dependent translational upregulation. Consequently, the β-secretase-cleaved C-terminal fragment of APP (C99) is also dramatically reduced in these mice. * p < 0.05 vs. wild-type, #
p < 0.05 vs. 5XFAD, §
p < 0.05 vs. BACE1+/− · NEP · 5XFAD. All data are presented as mean ± SEM.