Given that the detrimental effect of oxidative stress on the activity of α-secretase while elevated the expression and activation of β-secretase and γ-secretase, enzymes responsible for the generation of Aβ from APP56–60, our results indicate a contribution of EP/ROS/p38 MAP kinase signaling to amyloid pathology and abnormal Aβ/APP metabolism, possibly through APP processing and Aβ clearance. This evidence concerns the gene APP and amyloidosis.