a secreted apolipoprotein that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. Specific alleles influence the development of Alzheimer's Disease (AD). Humans express three alleles: APOE2, -E3 and -E4, and six genotypes — E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4. The E2 allele is the rarest form and reduces the risk of developing Alzheimer's. APOE3 is the most common allele and doesn't seem to influence AD risk. The E4 allele, present in approximately 10-15% of people, increases the risk for AD and lowers the age of onset. Having one copy of E4 can increase your risk 2 to 3 fold while two copies (E4/E4) can increase the risk 12 fold. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apoliproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues. APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting. APOE in also involved in innate and adaptive immune responses, controlling for instance the survival of myeloid-derived suppressor cells. Belongs to the apolipoprotein A1/A4/E family. Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph. Mainly synthesized by liver hepatocytes. Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus. It is also expressed by cells of the peripheral nervous system. Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues. Note: This description may include information from UniProtKB.
Protein type: Lipid-binding; Secreted; Secreted, signal peptide