APP and Alzheimer disease: Free radicals are thought to play a key role in promoting the development of AD and cognitive dysfunction in smokers, and oxidative stress regulates APP processing by altering β- and γ-secretase activity and promotes Aβ production through the JNK and PKR–eIF2α signaling pathways; cigarette smoking-associated cerebral oxidative stress is a potential mechanism that promotes AD pathology and increases the risk of AD [155,156].