Apolipoprotein E (APOE) is a class of apolipoprotein found in the chylomicron and Intermediate-density lipoprotein (IDLs) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. In peripheral tissues, APOE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism in an isoform-dependent manner. In the central nervous system, APOE is mainly produced by astrocytes, and transports cholesterol to neurons via APOE receptors, which are members of the low density lipoprotein receptor gene family.

The E4 variant is the largest known genetic risk factor for late-onset sporadic Alzheimer’s disease (AD) in a variety of ethnic groups. While the exact mechanism of how E4 causes such dramatic effects remains to be fully determined, evidence has been presented suggesting an interaction with amyloid. The isoform ApoE-ε4 is not as effective as the others at promoting these reactions, resulting in increased vulnerability to AD in individuals with that gene variation.