The big picture: The APOE gene instructs the body to produce a protein called apolipoprotein E that regulates cholesterol and fat levels in the blood and brain. It’s a well-studied genetic risk factor for cardiovascular disease and various neurological conditions like dementia, late on-set Alzheimer's disease, Parkinson’s and multiple sclerosis.

Genetic variants of APOE: There are three forms/alleles of the APOE gene: e2, e3, and e4. Each person inherits two copies of the APOE gene, one from each parent. The e3/e3 combination is the most prevalent. Notably, the e4 allele is associated with a substantially higher risk of cardiovascular diseases and dementia.

APOE and cardiovascular health: The e4 allele is often linked to elevated LDL cholesterol levels, increasing the risk of coronary heart disease by up to 46%. Conversely, the e2 allele is generally associated with lower LDL cholesterol levels. However, individuals with the e2/e2 genotype face a higher risk of peripheral artery diseases and a rare genetic condition called hyperlipoproteinemia type III which may lead to high triglyceride levels.

APOE and dementia: The e2 allele generally denotes a lower dementia risk, while the e4 allele indicates a higher risk. The e2/e3 genotype has the lowest risk for Alzheimer’s disease, and e2/e2 carries the lowest risk for all-cause dementia. The e4/e4 genotype significantly elevates the risk of Alzheimer's disease by 15x, with notable sex differences in risk levels for those carrying a single e4 allele: a 4x increased risk for women compared to a 2x risk for men.

APOE is NOT a deterministic gene: Importantly, possessing the e4 allele, whether in one or two copies, does not definitively lead to dementia or cardiovascular disease. Many with this genetic makeup do not develop these conditions.

Mitigating genetic risks: Actively maintaining optimal cholesterol and blood pressure levels can greatly reduce the risks associated with the APOE gene. Such proactive health measures are essential in managing genetic risks, particularly concerning cardiovascular health and Alzheimer’s disease.