Consistent with our previous study (Koffie et al., 2012), we observe a loss of synapses in Alzheimer's disease compared with control brain, the loss being exacerbated near plaques in APOE4 cases (one-way ANOVA, F(4.22) = 14.2, P < 0.0001, post hoc Tukey’s tests Alzheimer's disease APOE4 near versus far from plaques P = 0.032, control versus Alzheimer's disease APOE4 near P < 0.0001). Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.