The apolipoprotein E (ApoE) is involved in cholesterol and lipid metabolism in the brain, transporting cholesterol to neurons and removing lipid debris to facilitate myelin repair. ApoE4, one of three subtypes of ApoE, is the most important genetic risk factor for sporadic Alzheimer’s disease (AD). ApoE4 increases the deposition and reduces the clearance rate of Aβ, enhances hyperphosphorylation of Tau protein, induces abnormal lipid metabolism in the brain, and impairs the brain and blood-brain barrier. ApoE4 transgenic mice were used to study AD pathogenesis and prevention. ApoE4 transgenic mice showed decreased abilities in spatial learning and memory at the age of 9 months and a pathological phenotype related to β-amyloid at 2 ~ 4 months. At 4 months, total Tau and phosphorylated Tau levels increased, and a loss of neurons and damage to dendrites and synapses occurred in the hippocampus. ApoE4 transgenic mice have been used to study the prevention and treatment of AD drugs such as the GABA neuronal receptor agonist pentobarbital, the glutamine antagonist JHU-083, epidermal growth factor, inulin, and curcumin. This review provides a reference for those applying ApoE4 transgenic mice in AD research