ApoE peptide is neurotoxic in hippocampal cell cultures. A, Cultures were exposed for the indicated times to saline (Control), 2 μmapoE peptide (ApoEp), or 4 μm RAP plus 2 μm apoE peptide (RAP+ApoEp). The percentage of neurons surviving at each time point was quantified; values are the mean and SEM of determinations made in four separate cultures. *p < 0.05, **p < 0.01 compared with corresponding values in control and RAP + apoE cultures (ANOVA with Scheffe’s post hoc test). B, Cultures were exposed for 24 hr to the indicated concentrations of apoE peptide (ApoEp) in the absence (Control) or presence of 4 μmRAP. The percentage of neurons was quantified, and values are the mean and SEM of determinations made in four separate cultures. *p < 0.05, **p < 0.01 compared with corresponding values in RAP-treated cultures (ANOVA with Scheffe’s post hoc test). C, Phase-contrast micrographs of hippocampal neurons in a culture before treatment (A1), and 6 hr (A2) and 24 hr (A3) after exposure to 0.5 μm apoE peptide. B1 and B2 are micrographs of neurons in a culture before and 24 hr after exposure to saline, respectively. Note the degeneration of neuronal cell bodies (arrow) and neurites (arrowhead) in the culture exposed to the apoE peptide. (Figure 2continues.)