In this contest, JNK activation is well recapitulated in AD mouse models [95,96] where JNKs phosphorylate the amyloid precursor protein (APP) at the Thr668 site [124,125], inducing the amyloidogenic proteolytic processing and the production of Aβ toxic fragments in the brain parenchyma [126] (Figure 5). This evidence concerns the gene MAPK8 and Alzheimer disease.