Further downstream of PERK, ATF4 may also contribute to AD pathology; knockdown of Atf4 in axons exposed to oligomeric Aβ prevents the spreading of a degenerative signal across the mouse brain and subsequent neuronal cell loss, in part through the suppression of CHOP-mediated apoptotic signaling (Baleriola et al., 2014). This evidence concerns the gene DDIT3 and Alzheimer disease.