APOE and Alzheimer disease: We have previously reported a multi-omic analysis on an AD-vulnerable brain region (entorhinal cortex; EC) and an AD-resistant brain region (primary visual cortex; PVC) of aged APOE targeted replacement mice, which has thus far revealed novel effects of APOE4 expression on several important biological pathways, including neuronal activity [32], endosomal-lysosomal trafficking [33], and bioenergetics [34].