Differential Regulation of APP Secretion by Apolipoprotein E3 and E4

  • Benjamin Wolozin
  • Jasna Basaric-Keys
  • Robert Canter
  • Yunhua Li
  • Dudley Strickland
  • Trey Sunderland
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)


Apolipoprotein E (apo E) is a cholesterol transport protein that is present both in blood as well as in central nervous system, where its levels increase following nerve injury. Presumably the function of apo E is to facilitates lipid uptake1. In the periphery, apo E is synthesized by the liver and taken up throughout the body via low density lipoprotein receptors1. In the central nervous system, apo E is synthesized by astrocytes and microglial cells following nerve injury1. Apo E avidly binds lipids, in particular cholesterol, and it is taken up by the axon during regeneration2. Thus, the action of apo E plays an important role in the ability of the brain to cope with neuronal injury. This role may also be critical in the ability of the brain to cope with a neurodegenerative illness, such as Alzheimer’s disease.


PC12 Cell Neurite Outgrowth Amyloid Precursor Protein Neurite Extension Follow Nerve Injury 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    R. Mahley, (1988): Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology. Science 240:622–30.PubMedCrossRefGoogle Scholar
  2. 2.
    J. Boyles, C. Zoellner, L. Anderson, L. Kosik, R. Pitas, K. Weisgraber, D. Hui, R. Mahley, P. Gebicke-Haerter, M. Ignatius and E. Shooter, (1989): A role for apolipoprotein E, apolipoprotein A-1 and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J. Clin. Invest. 83:1015–31.PubMedCrossRefGoogle Scholar
  3. 3.
    W. Strittmatter, A. Saunders, D. Schmechel, M. Pericak-Vance, J. Enghild, G. Salvesen and A. Roses, (1993): Apolipoprotein E: high-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. PNAS 90:1977–81.PubMedCrossRefGoogle Scholar
  4. 4.
    E. Corder, A. Saunders, W. Strittmatter, D. Schmechel, P. Gaskell, G. Small, A. Roses, J. Haines and M. Pericak-Vance, (1993): Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–3.PubMedCrossRefGoogle Scholar
  5. 5.
    D. Schmechel, A. Saunders, W. Strittmatter, B. Crain, C. Hulette, S. Joo, M. Pericak-Vance, D. Goldgaber and A. Roses, (1993): Increased amyloid ß-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. PNAS 90:9649–53.PubMedCrossRefGoogle Scholar
  6. 6.
    G. Rebeck, J. Reiter, D. Strickland and B. Hyman, (1993): Apolipoprotein E in sporadic Alzheimer’s Disease: allelic variation and receptor interactions. Neuron 11:575–80.PubMedCrossRefGoogle Scholar
  7. 7.
    W. Strittmatter, K. Weisgraber, D. Huang, L. Dong, G. Salvesen, M. Pericak-Vance, D. Schmechel, A. Saunders, D. Goldgaber and A. Roses, (1993): Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. PNAS 90:8098–102.PubMedCrossRefGoogle Scholar
  8. 8.
    J. Ma, A. Yee, H. Brewer, S. Das and H. Potter, (1994): Amyloid-associated proteins alpha(1)-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 372:92–94.PubMedCrossRefGoogle Scholar
  9. 9.
    D. Loo, A. Copani, C. Pike, E. Whittemore, A. Walencewicz and C. Cotman, (1993): Apoptosis is induced by ß-amyloid in cultured central nervous system neurons. PNAS 90:7951–5.PubMedCrossRefGoogle Scholar
  10. 10.
    M. Reyland and D. Williams, (1991): Suppression of cAMP-mediated signal transduction in mouse adrenocortical cells which express apolipoprotein E. J. Biol. Chem. 266:21099–104.PubMedGoogle Scholar
  11. 11.
    T. Willnow, Z. Sheng, S. Ishibashi and J. Herz, (1994): Inhibition of hepatic chylomicron remnant uptake by gene transfer of a receptor antagonist. Science 264:1471–4.PubMedCrossRefGoogle Scholar
  12. 12.
    M. Ignatius, E. Shooter, R. Pitas and R. Mahley, (1987): Lipoprotein uptake by neuronal growth cones in vitro. Science 236:959–62.PubMedCrossRefGoogle Scholar
  13. 13.
    B. Wolozin, J. Basaric-Keys, R. Canter, Y. Li, D. VanderPutten and T. Sunderland, (1995): Differential regulation of APP secretion by apolipoprotein E3 and E4. Ann. New York Acad Sci. in press:.Google Scholar
  14. 14.
    D. Schubert, L. W. Jin, T. Saitoh and G. Cole, (1989): The regulation of amyloid ß protein precursor secretion and its modulatory role in cell adhesion. Neuron 3:689–694.PubMedCrossRefGoogle Scholar
  15. 15.
    S. Greenberg, E. Koo, D. Selkoe, W. Qiu and K. Kosik, (1994): Secreted ß-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation. Proc. Natl. Acad. Sci. (USA) 91:7104–8.CrossRefGoogle Scholar
  16. 16.
    B. Nathan, S. Bellosta, D. Sanan, K. Weisgraber, R. Mahley and R. Pitas, (1994): Differential effects of apolipoprotein E3 and E4 on neuronal growth in vitro. Science 264:850–2.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Benjamin Wolozin
    • 1
  • Jasna Basaric-Keys
    • 1
  • Robert Canter
    • 1
  • Yunhua Li
    • 1
  • Dudley Strickland
    • 2
  • Trey Sunderland
    • 1
  1. 1.Section on Geriatric PsychiatryNIMHBethesdaUSA
  2. 2.American Red Cross LabsRockvilleUSA

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