Consistent with many reports (Ma et al., 2013; Ma and Klann, 2014; Yang et al., 2016), our study showed that PERK and eIF2α were highly phosphorylated in the brains of 2 × Tg-AD mice, and long-term treatment of ECH dramatically decreased the phosphorylation of PERK and eIF2α, indicating that ECH inhibits ERS and the UPR by blocking PERK/eIF2α activation in vivo. This evidence concerns the gene EIF2AK3 and Alzheimer disease.