MAPK8 and Alzheimer disease: In early stages of AD, Aβ were reported to accumulate in post-synaptic areas leading to stimulation of pro-apoptotic pathways due to activation of the c-Jun N-terminal kinase (JNK) pathway; this results in phosphorylation of IRS1 at Serine residue 636 (pIRS1-Ser636), which renders IRS1 inactive and suppresses the stimulatory effect of insulin17.