APOE and Alzheimer disease: Despite that the past 30 years of tremendous efforts in research on AD have proposed a variety of hypotheses regarding pathological and biochemical manifestations (including amyloid, tau, cholinergic, excitotoxicity, oxidative stress, ApoE, CREB signaling pathways, etc.), the development of effective treatments for halting the progression of AD symptoms or curing AD has been fruitless because of the complex and multifactorial pathophysiology (Graham et al., 2017).