DAPT raises APP-CTF levels and lowers Aβ levels in brains of 4-month-old Ts65Dn mice.

Four-month-old Ts65Dn mice and wild type colony mate controls were treated with vehicle or DAPT (100 mg/kg/day) for 4 days. (A) Representative western blots of APP, CTFs and β-actin from control (ctrl) and Ts65Dn (Ts) mice. (B) Left panel, quantification of APP (Students t-test, mean±s.e.m.,unpaired, two-tailed, n = 8 per group). Ctrl+Vehicle vs. Ts+Vehicle, p = 0.0003; Ctrl+DAPT vs. Ts+DAPT, p = 0.0002; Ctrl+Vehicle vs. Ts+DAPT, p = 0.0001; Ctrl+DAPT vs. Ts+Vehicle, p = 0.0006. Right panel, combined (C99, C89 and C83) CTFs (all means differ significantly, n = 8, 1-way ANOVA, p = 0.0002; significant differences between individual pairs of mean calculated by Students t-test, mean±s.e.m., unpaired, two-tailed). (C) Aβ40 and Aβ42 quantification from control and Ts65Dn mice. Left panel, Aβ40 (Students t-test, mean±s.e.m., unpaired, two-tailed, n = 6 per group); Ctrl+Vehicle vs. Ts+Vehicle, p = 0.0173; Ctrl+Vehicle vs. Ctrl+DAPT, p = 0.0043; Ctrl+DAPT vs. Ts+Vehicle, p = 0.0079; Ts+Vehicle vs. Ts+DAPT, p = 0.0082. Right panel, Aβ42 (Students t-test, mean±s.e.m., unpaired, two-tailed, n = 6 per group); Ctrl+Vehicle vs. Ts+Vehicle, p = 0.0169; Ctrl+DAPT vs. Ts+Vehicle, p = 0.0003; Ts+Vehicle vs. Ts+DAPT, p = 0.0052.