Similar to the loss of synapses, evidence for ER stress in the form of the unfolded protein response (UPR) as signalled by activation of protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α) and activating transcription factor 6 (ATF6), has also been reported in the early stages of AD [20–22] and associated animal models [23–25]. The gene discussed is ATF6; the disease is Alzheimer disease.