There is an increase in the percentage of synaptic puncta co-localizing with both Aβ and clusterin in Alzheimer's disease APOE4 cases near plaques (Fig. 4D, Kruskal–Wallis test χ2(4) = 21.61, P = 0.0002, post hoc Mann–Whitney U between Alzheimer's disease APOE3 near and APOE3 far P = 0.0286, between Alzheimer's disease APOE4 near and APOE4 far P = 0.0006 and between Alzheimer's disease APOE3 near and Alzheimer's disease APOE4 near P = 0.0061). The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.