However, GCN2−/− and GCN2+/− deletion in 5XFAD mice unexpectedly aggravated the eIF2α phosphorylation-associated ATF4/CREB dysregulation as well as β-amyloidogenesis, thus failing to rescue the impairment of contextual learning and memory in this AD model. This evidence concerns the gene CREB1 and Alzheimer disease.