Two amino acids. That is all that separates the APOE2 and APOE4 versions of the apolipoprotein E gene, a difference so small it seems almost irrelevant. Yet carriers of APOE2 are dramatically more likely to reach their nineties and beyond, and they develop Alzheimer’s disease at a fraction of the rate of people who carry APOE4, which is the single largest genetic risk factor for the disease. For decades, researchers assumed the explanation had to involve cholesterol, since APOE’s main job is to.