Title: Apolipoprotein E
Additional Names: ApoE
Literature References: Protein component of several classes of lipoproteins; plays a central role in plasma lipoprotein metabolism and cholesterol transport. Also involved in lipid-transport in the development and repair of nervous tissue. Polymorphic glycoprotein containing 299 amino acid residues; mol wt 34.2 kDa. Three major isoforms have been identified in humans (apo-E2, E3, E4) which are the product of 3 independent alleles (e2, e3, e4) at a single gene locus. The isoforms differ from each other only in cysteine-arginine interchanges at 2 substitution sites. Allele e3 is the most common; inheritance of e4 has been associated with increased risk of Alzheimer's disease. Primarily synthesized in the liver by parenchymal cells and in the brain by astrocytes. Also produced in significant amounts by mature macrophages. Discovery as component of VLDL: V. G. Shore, B. Shore, Biochemistry 12, 502 (1973). Purification and characterization: V. I. Zannis, J. L. Breslow, Mol. Cell. Biochem. 42, 3 (1982). Amino acid sequence: S. C. Rall, Jr. et al., J. Biol. Chem. 257, 4171 (1982). Biosynthesis and activity: R. W. Mahley, Science 240, 622 (1988). Association with Alzheimer's disease: A. M. Saunders et al., Neurology 43, 1467 (1993); L. A. Farrer et al., J. Am. Med. Assoc. 278, 1349 (1997). Review of role in lipoprotein metabolism: A. D. Dergunov, M. Rosseneu, Biol. Chem. Hoppe-Seyler 375, 485-495 (1994); P. de Knijff et al., Hum. Mutat. 4, 178-194 (1994). Review of role in the nervous system: J. Poirier, Trends Neurosci. 17, 525-530 (1994); K. H. Weisgraber et al., Curr. Opin. Lipidol. 5, 110-116 (1994); R. W. Mahley et al., ibid. 6, 86-91 (1995).