Fig. 6.

Visual function is protected in anti-Aβ40/42–treated APOE4-HFC mice in a dose-dependent fashion that correlates with plasma levels of Aβ. (A) Dose-response study of ERG b-wave recovery in APOE4-HFC mice treated with three different doses of the anti-Aβ40/42 antibody. Baseline b-wave amplitudes are a function of flash intensity obtained from APOE4-ND controls (black, ND) and APOE4-HFC controls (green, HFC). As shown in Fig. 1A, b-wave amplitudes in the 3-mg/kg anti-Aβ40/42 antibody-treated APOE4-HFC animals (red, HFC 3 mg/kg) were fully preserved. In contrast, b-wave amplitudes in the 0.3- and 0.03-mg/kg anti-Aβ40/42 antibody-treated APOE4-HFC mice (olive green, HFC 0.3 mg/kg; blue, HFC 0.03 mg/kg, respectively) decreased to the same level as vehicle-treated APOE4-HFC animals (data are expressed as mean ± SEM). (B and C) Dose-dependent increase in plasma levels of Aβ and anti-Aβ40/42. Weekly i.p. injections of anti-Aβ40/42 at 0 (vehicle), 0.03, 0.3, and 3 mg/kg produced a statistically significant, dose-dependent increase in the plasma levels of total (bound and unbound) Aβ (B) that correlated with a dose-dependent increase in the concentrations of plasma anti-Aβ40/42 antibodies (C). Significant difference indicating a dose-dependent elevation of plasma (Aβ and anti-Aβ40/42) after increasing dose of antibody was shown by one-way ANOVA (P < 0.0001) and the posttest for linear trend (i.e., dose-dependent change), which was significant at P < 0.0001. In addition, there is a statistically significant increase in total Aβ plasma levels in response to the HFC diet compared with ND (*P < 0.05; B). Error bars represent SD.