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Apolipoprotein E (APOE), a main apoprotein of the chylomicron, binds to a specific receptor on liver cells and peripheral cells. APOE is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. APOE was initially recognized for its importance in lipoprotein metabolism and cardiovascular disease. More recently, it has been studied for its role in several biological processes not directly related to lipoprotein transport, including Alzheimer's disease, immunoregulation, and cognition. Defects in APOE result in familial dysbetalipoproteinemia, or type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron, VLDL and LDL remnants.
The APOE protein is 299 amino acids long 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 receptors for APOE.
The APOE gene, APOE, is mapped to chromosome 19 in a cluster with Apolipoprotein C1 and Apolipoprotein C2. APOE consists of four exons and three introns, totaling 3597 base pairs. The gene is polymorphic, with three major alleles, APOE2, APOE3, APOE4, which translate into three isoforms of the protein: normal - APOE-ε3; dysfunctional - APOE-ε2 and APOE-ε4. These isoforms differ from each other only by single amino acid substitutions at positions 112 and 158, but have profound physiological consequences. E2 is associated with the genetic disorder type III hyperlipoproteinemia and with both increased and decreased risk for atherosclerosis. E4 has been implicated in atherosclerosis and Alzheimer's disease, impaired cognitive function, and reduced neurite outgrowth.
Alzheimer's Disease (AD)Edit
APOE-ε4 has been shown to cause an increased susceptibility to AD. 40-65% of AD patients have at least one copy of the 4 allele. There is also evidence that the 2 allele may serve a protective role.
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