Apolipoprotein-E (ApoE) is composed of 299 amino acids and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood. It is synthesized principally in the liver, but has also been found in other tissues such as the brain, kidneys, and spleen. In the nervous system, non-neuronal cell types, most notably astroglia and microglia, are the primary producers of ApoE, while neurons preferentially express the ApoE receptors. There are seven currently identified mammalian receptors for ApoE which belong to the evolutionarily conserved low density lipoprotein receptor gene family.
People with harmful forms of the ApoE gene (genotype 3/4, 4/4) have up to 12 times the risk of developing Alzheimer's disease compared with those who have other variations (2/2, 2/3, 3/3) of the gene. Another role of ApoE is in the removal of mercury from the biosystem. The optimal genotype for removing mercury is ApoE 2/2 (4 cysteine residues),whereas ApoE 3/3 is the most prevalent in the human population (2 cysteine residues and 2 arginine residues), and the most detrimental is ApoE 4/4 (4 arginines and no mercury removing capability).