Mechanisms by which STZ-induced insulin deficiency elevates BACE1 levels in 5XFAD mice.

<p>(<i>A</i>) Real-time qPCR revealed no difference in BACE1 mRNA levels between STZ- and vehicle-treated 5XFAD mouse brains (<i>n</i> = 4–5 mice per group). (<i>B, E</i>) Western blot analysis of hemibrain lysates from vehicle- and STZ-treated 5XFAD mice. Immunoreactive bands for phosphorylated eIF2α (p-eIF2α) and total eIF2α (<i>C</i>), phosphorylated PERK (p-PERK) (<i>D</i>), and the 17-kDa fragment of activated caspase-3 and GGA3 (<i>F</i>) were quantified and expressed as the percentage of vehicle-treated 5XFAD levels (<i>n</i> = 4–7 mice per group). Levels of p-eIF2α, but not those of total eIF2α, were significantly elevated in STZ-treated 5XFAD mice (*<i>p</i><0.05 vs. vehicle). STZ treatments also dramatically increased p-PERK levels in 5XFAD mice (<i>p</i> = 0.05), while cleaved caspase-3 and GGA3 levels were indistinguishable between STZ- and vehicle-treated subjects. All data are presented as mean ± SEM.