APOE and Alzheimer disease: While early work investigating the association between APOE ε4 (APOE4) and AD focused on the ability of APOE4 to increase the aggregation and decrease the clearance of amyloid beta (Aβ) [1–7], more recent work has uncovered numerous effects of differential APOE isoform expression on other AD-relevant systems in the brain, including intracellular trafficking, energy metabolism, inflammation, and vascular integrity [see reviews by [8–11]].