Apolipoprotein E

  • Catalog Number: A70105
  • Price: $285/L

Apolipoprotein E (Apo E) is a member of the apolipoprotein family which are carrier proteins that combine with lipids to for lipoprotein molecules. Lipoproteins are responsible for packaging cholesterol and other fats, transporting them through the blood stream, and delivering them to appropriate locations for further processing. Apo E is essential for normal catabolism of triglyceride-rich lipoprotein constituents. Apo E specific interaction with low density lipoprotein (LDL)-receptor is an essential mechanism controlling the removal of excess cholesterol from the blood and carry it to the liver for processing. thus determines the homeostatis of cholesterol and triglycerides.

Apo E has been recognized for its important roles in lipoprotein metabolism and cardiovascular disease. It is now more recently, studied for its role in lipoprotein transport and Alzheimer's disease, and many other biological functions such as aging. In humans, it is mainly synthesized in the liver, it functions to transport triglycerides to liver tissue. and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood.

It is also associated with HDL and functions in cholesterol distribution. When incorportated intestinal cholymicrons, transports dietary triglycerides and cholesterol.

Apo E is 299 amino acids long with a molecular weight of approximately 34 kDaltons. Normal serum levels are approximately 5-8 mg/dL. This takes on a biologically redundant presences since it has been estimated that only 0.4mg/dL is efficient to clear cholesterol from the blood stream. (hasty et. al.) In plasma, 90% of the protein is desialyated. Apo E plasma concentration levels in healthy individuals may vary with respect to different biological functions. Sex, age, and lifestyle contribute to trends of concentrations. When Apo E is expressed at very high levels, serum cholesterol levels are also increased due to the competitive nature of free Apo E with lipoprotein bound-Apo E for hepatic receptors.(Hasty) Hyperlipidemia is also associated with defective or defeicien Apo E. Apo E levels ranging from 0.4 mg/dL to approximately 8 mg/dL are compatible with complete plasma cholesterol homeostatsis.

Apo E redistributes lipids among different tissues. Transfers lipids from synthesized areas to storage areas. Since directly involved in uptake and distribution of plasma lipids, has several implications for cardiovascular disease. Apo E also important role in inhibition of platelet aggregation.

In association with Alzheimer's disease, Apo E regulates protein A levels in the brain. Research studies have associated the accumulation and deposition of neuron-damaging clumps of protein A as a primary characteristic of Alzheimer's disease. Varies isoforms of Apo E have varying ability to promote Protein A degredation. Certain isotypes of ApoE seem to increase the risk for developing Alzheimers. Apo E gene is polymorphic, with three common alleles (E2, E3, E4). These isoforms differ in a single amino acid substitution and in their affinity for LDL- receptors. Apo E2 allele is associated with lower plasma cholesterol concentrations while the E4 allele is associated with higher levels. E4 has also been suggested to increase an idividual's risk for developing type 2 Alzheimer disease. Researchers have found that the Apo E4 allele is associated with an increased number of protein clumps, called amyloid plaques, in the brain tissue of people with Alzheimer disease. (genetics home reference) The Apo E genotype is suggested as a determinant risk factor for certain diseases such as cardiovascular disease and alzheimers. Serum levels of andorogens and DHEA are associated with the Apo E genotype in postmenopausal women. Apo E2 and E3 genotype in perimenopausal womean appear to improve plasma lipoprotein-lipid profiles more with hormone replacement therapy than Apo E4 women (Hagberg et. al).

Plasma concentration in association with Apo E genotype may yield useful laboratory information. The relationship between Apo E genotype and plasma concentration may be significantly influenced by age, sex, and body weight distribution. Futher suggest the "epigenetic role" regarding gene-environment interactions.

Literature Cited:
  1. J. Hasburg, K. Wilund, R. Ferrell. 2000. Apo E gene and gene-environment effects on plasma lipoprotein-lipid levels. Physiol Genomics 4: 101-108.
  2. A. Hasty, M. F. Linton, L. L. Swift, S. Fazio. 1999. Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance. J. of Lipid Research 40: 1529-1538.
  3. I. Zofkova, K. Zajickova, M. Hill, A. Horinek. 2002. Apolipoprotein E gene determines serum testoerone and dehydroepiandrosterone levels in postmenopausal women. Euro J. or Endo. 147: 503-506.
  4. G. Siest, T. Pillot, A. Regis-Bailly, B. Leininger-Muller, J. Steinmetz, M. Galteau, S. Visvikis. 1995. Apolipoprotein E: An Important Gene and Protein to Follow in Laboratory Medicine. Clin. Chem. 41: 1098-1086.