APOE and Alzheimer disease: Further, there is a significant drop in pre-synaptic density near plaques when compared with far from plaques in Alzheimer's disease cases (two-way ANOVA effect of plaque distance, F (1, 18) = 11.21, P = 0.0036) and a significant effect of APOE genotype on synapse density (two-way ANOVA effect of APOE genotype, F (1, 18) = 16.67, P = 0.0007, Fig. 4A).