APOE and Alzheimer disease: Building upon our transcriptomics findings and to determine whether endosomes are similarly affected by APOE4 expression in the absence of overt AD pathology, we investigated the endosomal–lysosomal system in the brains of 18-month-old APOE4/4 vs. APOE3/3 targeted replacement mice, as has been done in human tissue (Cataldo et al., 2000).