Apolipoprotein E Uptake is Increased by Beta-Amyloid Peptides and Reduced by Blockade of the LDL Receptor

  • Uwe Beffert
  • Nicole Aumont
  • Doris Dea
  • Jean Davignon
  • Judes Poirier
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

Apolipoprotein E (apoE) is a lipid-binding, 37 kDa, 299 amino acid glycoprotein involved in cholesterol and phospholipid transport and metabolism. ApoE mediates the uptake of lipid complexes through interaction with the apoB/ApoE (LDL) receptor and other receptors1. The LDL receptor pathway consists of cell surface binding of apoE-containing lipoproteins followed by internalization and degradation of the lipoprotein by a lysosomal pathway2. In the peripheral nervous system, apoE has been proposed to be involved in the transport of cholesterol in repair, growth and maintenance of membranes during development or following injury3,4. In the central nervous system, ApoE released from astrocytes in response to injury such as entorhinal cortex lesions in the rat plays a pivotal role in the redistribution of cholesterol and phospholipids during synaptic remodeling and compensatory synaptogenesis5,6.

Keywords

Primary Neuronal Culture Cell Surface Binding Cholinergic Dysfunction Human apoE3 Allele Copy Number 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. Poirier. Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease, Trends Neurosci 17:525–530. (1994).PubMedCrossRefGoogle Scholar
  2. 2.
    J.L. Goldstein, S.K. Basu and M.S. Brown. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells, Methods Enzymol 98:241–260. (1983).PubMedCrossRefGoogle Scholar
  3. 3.
    J.K. Boyles, C.D. Zoellner, L.J. Anderson, L.M. Kosik, R.E. Pitas, K.H. Weisgraber, D.Y. Hui, R.W. Mahley, P.J. Gebicke-Haerter, M.J. Ignatius and E.M. Shooter. A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve, J Clin Invest 83:1015–1031.(1989).PubMedCrossRefGoogle Scholar
  4. 4.
    J. K. Boyles, L.M. Notterpek and L.J. Anderson. Accumulation of apolipoproteins in the regenerating and remyelinating mammalian peripheral nerve. Identification of apolipoprotein D, apolipoprotein A-IV, apolipoprotein E, and apolipoprotein A-I, J Biol Chem 265:17805–17815. (1990).PubMedGoogle Scholar
  5. 5.
    J. Poirier, M. Hess, P.C. May and CE. Finch. Astrocytic apolipoprotein E mRNA and GFAP mRNA in hippocampus after entorhinal cortex lesioning, Brain Res Mol Brain Res 11:97–106. (1991).PubMedCrossRefGoogle Scholar
  6. 6.
    J. Poirier, A. Baccichet, D. Dea and S. Gauthier. Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats, Neuroscience 55:81–90. (1993).PubMedCrossRefGoogle Scholar
  7. 7.
    J. Davignon, R.E. Gregg and C.F. Sing. Apolipoprotein E polymorphism and atherosclerosis, Arteriosclerosis 8:1–21. (1988).PubMedCrossRefGoogle Scholar
  8. 8.
    J. Poirier, J. Davignon, D. Bouthillier, S. Kogan, P. Bertrand and S. Gauthier. Apolipoprotein E polymorphism and Alzheimer’s disease, Lancet 342:697–699. (1993).PubMedCrossRefGoogle Scholar
  9. 9.
    A.M. Saunders, W.J. Strittmatter, D. Schmechel, P.H. George-Hyslop, M.A. Pericak-Vance, S.H. Joo, B.L. Rosi, J.F. Gusella, D.R. Crapper-MacLachlan, M.J. Alberts, C. Hulette, B. Crain, D. Goldgaber and A.D. Roses. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease, Neurology 43:1467–1472. (1993).PubMedCrossRefGoogle Scholar
  10. 10.
    E.H. Corder, A.M. Saunders, W. J. Strittmatter, D.E. Schmechel, P.C. Gaskell, G.W. Small, A.D. Roses, J.L. Haines and M.A. Pericak-Vance. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families [see comments], Science 261:921-923. (1993).Google Scholar
  11. 11.
    J. Nalbantoglu, B.M. Gilfix, P. Bertrand, Y. Robitaille, S. Gauthier, D.S. Rosenblatt and J. Poirier. Predictive value of apolipoprotein E genotyping in Alzheimer’s disease: results of an autopsy series and an analysis of several combined studies, Ann Neurol 36:889–895. (1994).PubMedCrossRefGoogle Scholar
  12. 12.
    Y. Namba, M. Tomonaga, H. Kawasaki, E. Otomo and K. Ikeda. Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jakob disease, Brain Res 541:163–166. (1991).PubMedCrossRefGoogle Scholar
  13. 13.
    T. Wisniewski, B. Frangione. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid, Neurosci Lett 135:235–238. (1992).PubMedCrossRefGoogle Scholar
  14. 14.
    J. Poirier, I. Aubert, P. Bertrand, R. Quirion, S. Gauthier, J. Nalbantoglu. Apolipoprotein E4 and cholinergic dysfunction in Alzheimer’s disease. In: Giacobini E, Becker R, eds. Advances in Alzheimer Therapy. Boston: Birkhauser, (1994).Google Scholar
  15. 15.
    D.E. Schmechel, A.M. Saunders, W.J. Strittmatter, B.J. Crain, CM. Hulette, S.H. Joo, M.A. Pericak-Vance, D. Goldgaber and A.D. Roses. Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease, Proc Natl Acad Sci USA 90:9649–9653. (1993).PubMedCrossRefGoogle Scholar
  16. 16.
    U. Beffert, J. Poirier. Apolipoprotein E, plaques, tangles and cholinergic dysfunction in Alzheimer’s disease. Ann NY Acad Sci (In Press).Google Scholar
  17. 17.
    W.J. Strittmatter, K.H. Weisgraber, D.Y. Huang, L.M. Dong, G.S. Salvesen, M. Pericak-Vance, D. Schmechel, A.M. Saunders, D. Goldgaber and A.D. Roses. Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease, Proc Natl Acad Sci USA 90:8098–8102. (1993).PubMedCrossRefGoogle Scholar
  18. 18.
    J.B. Mitchell, K. Betito, W. Rowe, P. Boksa and M.J. Meaney. Serotonergic regulation of type II corticosteroid receptor binding in hippocampal cell cultures: evidence for the importance of serotonin-induced changes in cAMP levels, Neuroscience 48:631–639. (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    L. Brissette, P.D. Roach and S.P. Noel. The effects of liposome-reconstituted apolipoproteins on the binding of rat intermediate density lipoproteins to rat liver membranes, J Biol Chem 261: 11631–11638. (1986).PubMedGoogle Scholar
  20. 20.
    C.E. Matz, A. Jonas. Micellar complexes of human apolipoprotein A-I with phosphatidylcholines and cholesterol prepared from cholate-lipid dispersions, J Biol Chem 257:4535–4540. (1982).PubMedGoogle Scholar
  21. 21.
    U.K. Laemmli. Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227:680–685. (1970).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Uwe Beffert
    • 1
  • Nicole Aumont
    • 1
  • Doris Dea
    • 1
  • Jean Davignon
    • 2
  • Judes Poirier
    • 1
  1. 1.Douglas Hospital Research Centre, McGill Centre for Studies in Aging, Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  2. 2.Clinical Research Institute of MontrealMontrealCanada

Personalised recommendations