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Apolipoprotein E (apoE) is a major constituent of lipoproteins in the plasma and in the brain. There are three common apoE isoforms, termed E2, E3, and E4. By virtue of its ability to bind to lipoprotein receptors, apoE plays a key role in the metabolism of triglyceride-rich lipoproteins in the plasma. Homozygous carriers of apoE2 have an increased risk to develop type III hyperlipoproteinemia, whereas apoE4 is associated with elevated levels of low-density lipoprotein cholesterol. In the brain, apoE is associated with cholesterol-rich lipoproteins and is involved in the transport of cholesterol to neurons. The genetic polymorphism of apoE is among the strongest determinants of the risk and mean age of onset of Alzheimer's disease. The mechanism by which apoE isoforms differentially contribute to disease expression is not known.