Time- and dose/concentration-dependent inhibition of Aβ generation in plasma and brain of C57BL/6 mice. Time- and dose-dependent inhibition of Aβ generation in C57BL/6 mice after a 25 μmol/kg (diamonds), 50 μmol/kg (squares), 100 μmol/kg (triangles), or 200 μmol/kg (filled circles) oral dose. Mean ± SD observed and fitted time-plasma exposure profiles (A). Mean ± SD observed and fitted time-Aβ40 in brain profiles (B). Plasma exposure versus observed mean ± SD and fitted Aβ40 in brain (C). Mean ± SD observed and fitted time-Aβ42 in brain profiles (D). Unbound plasma versus free brain concentrations as measured in individual mice at the different doses and time points (E). Only values above LLOQ are shown, the mean levels (±SEM, n = 59) of Aβ40 and Aβ42 in the vehicle-treated groups were 4352 ± 136 and 1072 ± 31 pg/g tissue, respectively. The effect on sAPPβ was also studied and displayed maximum reduction at 6 h after a 100 μmol/kg dose (F). Data are presented as mean values ± SEM (**p < 0.01, compared with vehicle).