Explainer: What is APOE4 and how does it relate to Alzheimer’s disease?

APOE4 is the strongest risk factor for late-onset Alzheimer’s, the most common form of the disease that develops after the age of 65, according to the National Institutes of Health. The disease afflicts more than 6 million people in the United States.

It is one of three forms of the apolipoprotein E gene, which encodes instructions for a protein that carries cholesterol around the bloodstream. Three decades ago, scientists discovered that the gene also plays a role in Alzheimer’s risk, though exactly how is still not clear.

Everyone has two copies of the APOE gene, one inherited from each parent. APOE3 is the most common, and does not raise Alzheimer’s risk. APOE2, which is rare, may be protective against the disease.

APOE4 increases Alzheimer’s risk and is linked with an earlier onset of the disease. Some 25 percent of people have one copy of APOE4 and 2-5 percent have two copies.

Children of a parent with two copies of the APOE4 variant are presumed to have at least one copy, increasing their own risk.