Aβ deposition activates the MAPK cascade, including JNK, ERK, and p38, consequently inducing NF-κB activation, leading to glutamate excitability toxicity, synaptic plasticity disruption, proinflammatory cytokine production, and neuronal apoptosis, manifesting as cognitive dysfunction such as spatial learning and memory impairments in a rat model of AD. This evidence concerns the gene MAPK8 and Alzheimer disease.