Apolipoprotein E: Paradoxes Abound

Abstract

Apolipoprotein E was so dubbed two decades ago when apolipoproteins were being named in alphabetical sequence as their properties were detailed (apo E was first characterized as the “arginine-rich” peptide). Subsequently its properties have been virtually completely described^1,2: it is a peptide composed of 299 amino acids with a molecular weight of 34,000 daltons. It contains 22 amino acid repeats, forming amphipathic helices. It is synthesized primarily in the liver (though it is virtually ubiquitous in tissues, recently receiving special notoriety because of its distribution in the central nervous system in the areas of injury, and, specifically, its concentration in the plaques of the brains of patients with Alzheimer’s disease). It is secreted in glycosylated form and is a constituent of all plasma lipoprotein classes (chylomicrons, very low density lipoproteins [VLDL], intermediate density lipoproteins [IDL], and high density lipoproteins [HDL]) except low density lipoproteins (LDL) (though traces of apo E may be found in more buoyant LDL particles, especially in animal species other than the human). Like apo B, it serves as a ligand for the E/B (LDL) receptor, and its binding domain has been characterized in detail. It has also been reported to constitute the principal apolipoprotein ligand for the apo E (“chylomicron”) receptor in the liver, which has otherwise been characterized as the lipoprotein receptor protein (LRP). The gene that codes for apo E has been sequenced, cloned, and localized on chromosome 19 at the C 19q13.1 locus, closely linked to the apo C-I and apo C-II genes and more remotely linked to the gene for the LDL receptor.