Variants of apolipoprotein E have been studied extensively as risk factors for many different conditions. For example, APOE alleles have been shown to influence the risk of cardiovascular diseases. People who carry at least one copy of the APOE e4 allele have an increased chance of developing atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. This progressive narrowing of the arteries increases the risk of heart attack and stroke. 
 
 The APOE e2 allele has been shown to greatly increase the risk of a rare condition called hyperlipoproteinemia type III. Most people with this disorder have two copies of the APOE e2 allele, leading researchers to conclude that the e2 allele plays a critical role in the development of the condition. Hyperlipoproteinemia type III is characterized by increased blood levels of cholesterol, certain fats called triglycerides, and molecules called beta-very low-density lipoproteins (beta-VLDLs), which carry cholesterol and lipoproteins in the bloodstream. A buildup of cholesterol and other fatty materials can lead to the formation of small, yellow skin growths called xanthomas and the development of atherosclerosis. 
 
 APOE gene variants have also been studied as a potential risk factor for age-related macular degeneration, an eye disease that is a leading cause of vision loss among older people worldwide. Some studies have suggested that having at least one copy of the APOE e4 allele may help protect against this disease or delay the onset of vision loss, while having at least one copy of the APOE e2 allele may increase the risk of this disease or cause symptoms to appear earlier. However, other studies have not found these associations. More research is needed to clarify what role, if any, APOE gene variants play in the development of age-related macular degeneration. ||||| The gene comes in three varieties, known as the e2, e3 and e4 variants. Since everyone inherits one version of the gene from each parent, there are six possible combinations. People with one — and especially two — e4 variants are significantly more likely to develop Alzheimer's than people without e4. Researchers also have found that adults with e2 variants have more plaques in their brains but are less likely to have symptoms of dementia.
– You have one of six possible variations of the APOE gene, having inherited one variant—e2, e3, or e4—from each parent. Reporting in the journal Neuron, University of Hawaii researchers found that the brain development of children as young as preschool age with two copies of e4 or one of e4 and one of e2 seem most adversely affected—an intriguing find in light of previous research that has linked the e4 variant to Alzheimer's. Researchers scanned the brains of 1,187 healthy people between the ages of 3 and 20 and found, for instance, that the size of the hippocampus tends to be smaller in those with the e2/e4 combination. They also found some kids with e4 didn't perform as well on tests of memory, though they caught up with their peers by age 10, reports HealthDay News. And while brain researcher Rebecca Knickmeyer, who didn't participate in the study but wrote an accompanying editorial, says the variants aren't necessarily predictive and people shouldn't start testing their kids, the research suggests that Alzheimer's may in fact be a developmental disorder, not strictly an aging one, reports the Los Angeles Times. That raises the possibility that adjustments to "diet or cognitive training" early on could change someone's "trajectory," per Knickmeyer. Three in four people have at least one copy of e3, which seems to offer a protective effect. About 14% of people have an e4 variant, which has been linked with an elevated risk of Alzheimer's, but Knickmeyer points out that there are many Alzheimer's patients without e4, and many with e4 who never develop Alzheimer's. (Some research suggests that memories lost to Alzheimer's are actually retrievable.)