eIF2α phosphorylation is elevated in brains of Alzheimer's disease (AD) patients and in AD mouse models37, 38, 39, 40, and genetic deletion or haploinsufficiency of the eIF2α kinase PERK prevented enhanced eIF2α phosphorylation and deficits in protein synthesis, as well as synaptic plasticity defects, memory deficits and cholinergic neurodegeneration37, 38. Here, EIF2AK3 is linked to early-onset autosomal dominant Alzheimer disease.