APOE and Alzheimer disease: However, although numerous studies [10–14] document that APOE-e4 increases the relative risk of Alzheimer disease (compared to no copies of APOE-e4, there is a 2- to 4-fold increase in risk for one copy of APOE-e4, and an 8-to 15-fold increase for two copies), its effect on absolute risk is less clear.