APOE and Alzheimer disease: The inheritance of two copies of APOE4 increases the chance of developing AD by 12 times compared to the risk of a person with two copies of APOE3. Homozygous APOE4 carriers who develop AD also have a lower average age of clinical onset of 68 years of age compared to an average age of onset of 84 for an individual with two copies of APOE3. One copy of APOE4 increases the chance of AD by three times and lowers the average age of onset to 76 years of age 1.