The goal of this study was to evaluate the activity of long-term ARB treatment at modulating AD-relevant pathology in mice that express human APOE4. Our data demonstrate that ARB treatment is beneficial for memory-relevant behavior, hippocampal synaptic protein levels, and neuroinflammation in female mice that express APOE4 both in the presence (E4FAD+) and absence (E4FAD−) of high Aβ levels. This evidence concerns the gene APOE and Alzheimer disease.