Apolipoprotein E4, Cholinergic Integrity, Synaptic Plasticity and Alzheimer’s Disease

  • J. Poirier
  • M.-C. Delisle
  • R. Quirion
  • I. Aubert
  • J. Rocheford
  • I. Rousse
  • S. Gracon
  • M. Farlow
  • S. Gauthier
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)

Summary

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the hippocampal response to injury. The coordinated expression of apoE and its receptor, the apoE/apoB (LDL) receptor, appears to regulate the transport of cholesterol and phospholipids during the early and intermediate phases of the reinnervation process. During dendritic remodelling and synaptogenesis, neurons progressively repress the synthesis of cholesterol in favor of choles terol internalization through the apoE/LDL receptor pathway. The discovery that the apolipoprotein E4 allele is strongly linked to both sporadic and familial late onset Alzheimer’s disease (AD) raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the central nervous system is particularly important in relation to the function of the cholinergic system, which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence indicates that the apoE4 allele has a direct impact on cholinergic function and on cholinomimetic drug response in AD subjects.

Keywords

Cholesterol Polypeptide Neurol Choline Acetylcholine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aubert I, Araujo DM, Cécyre D, Robitaille Y, Quirion R (1992) Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer’s and Parkinson’s diseases. J Neurochem 58: 529–541PubMedCrossRefGoogle Scholar
  2. Beffert U, Poirier J (1995) Apolipoprotein E, plaques, tangles and cholinergic dysfunction in Alzheimer’s disease. Ann NY Acad Sci, in pressGoogle Scholar
  3. Bertrand P, Oda T, Finch CE, Pasinetti GM, Poirier J (1995) Association between apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer’s disease. Mol Br Res, in pressGoogle Scholar
  4. Boyles JK, Zoellner CD, Anderson LJ, Kosick LM, Pitas RE, Weisgraber KH, Hui DY, Mahley RW, Gebicke-Haeter PJ, Ignatius MJ, Shooter EM (1989) A role for apolipoprotein E, apolipoprotein A-l, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J Clin Invest 83: 1015–1031PubMedCrossRefGoogle Scholar
  5. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 and risk of Alzheimer’s disease in late onset families. Science 261: 921–923PubMedCrossRefGoogle Scholar
  6. Davignon J, Gregg RE, Sing CF (1988) Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8: 1–21PubMedCrossRefGoogle Scholar
  7. Davies P, Maloney AJR (1976) Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 2: 1403PubMedCrossRefGoogle Scholar
  8. Dawson RM (1989) Tacrine slows the rate of ageing of sarin-inhibited acetylcholine esterase. Neurosci Lett 100: 227–230PubMedCrossRefGoogle Scholar
  9. Elshourbagy NA, Liao WS, Mahley RW, Taylor JM (1985) Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc Natl Acad Sci 82: 203–207PubMedCrossRefGoogle Scholar
  10. Etienne P, Robitaille Y, Wood P, Gauthier S, Nair NPV, Quirion R (1986) Nucleus basalis neuronal loss and choline acetyltransferase activity in advanced Alzheimer’s disease. Neuro-science 4: 1279–1291Google Scholar
  11. Farlow M, Gracon SI, Hershey LA, Lewis KW (1992) A controlled trial of tacrine in Alzheimer’s disease. JAMA 268: 2523–2529PubMedCrossRefGoogle Scholar
  12. Guillaume D, Dea D, Davignon J, Poirier J (1995) Low density lipoprotein pathways in the central nervous system and apolipoprotein E isoform-specific differences. In: Iqbal K, Mortimer JA, Winblad B, Wisniewski H (eds) Research advances in Alzheimer’s disease and related disorders. John Wiley and Sons, pp 384–395Google Scholar
  13. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL (1984) Alzheimer’s disease: cell-specific pathology isolates the hippocampal formation. Science 225: 1168–1170PubMedCrossRefGoogle Scholar
  14. Knapp MJ, Knopman DS, Solomon DR (1994) A 30-week randomized controlled clinical trial of high doses of tacrine in patients with Alzheimer’s disease. JAMA 271: 985–991PubMedCrossRefGoogle Scholar
  15. LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Gertz GS (1994) Isoform-specific binding of apolipoprotein E to ßamyloid. J Biol Chem 269: 23403–23406PubMedGoogle Scholar
  16. Masliah E, Mallory M, Alford M, Mucke L (1995) Abnormal synaptic regeneration in APP695 transgenic and apoE knockout mice. In: Iqbal K, Mortimer JA, Windblad B, Wisniewski HM (eds) Research advances in Alzheimer’s disease and related disorders. Wiley J and Sons, 405–414Google Scholar
  17. Morris RGM, Garrud P, Rawlings J, O’Keefe J (1982) Place navigation impaired in rats with hippocampal lesions. Nature 297: 681–683PubMedCrossRefGoogle Scholar
  18. Namba Y, Tomonaga M, Kawasaki H (1991) Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and in Creutzfeldt-Jacob disease. Brain Res 541: 163–166PubMedCrossRefGoogle Scholar
  19. Nitsch RM, Blusztajn JK, Pitas AG, Slack BE, Wurtman PJ (1992) Evidence for a membrane defect in Alzheimer’s disease. Proc Natl Acad Sci USA 89: 1671–1675PubMedCrossRefGoogle Scholar
  20. Nöguchi S, Murakami K, Yamada N (1993) Apolipoprotein E and Alzheimer’s disease. Lancet (Letter) 342: 737CrossRefGoogle Scholar
  21. Payami H, Kaye J, Heston LL, Schellenberg GD (1993) Apolipoprotein E and Alzheimer’s disease. Lancet (letter) 342: 738CrossRefGoogle Scholar
  22. Perry EK, Gibson PH, Blessed G (1977) Neurotransmitter enzyme abnormalities in senile dementia. J Neurol Sci 34: 247–265PubMedCrossRefGoogle Scholar
  23. Poirier J (1994) Apolipoprotein E in animal models of brain injury and in Alzheimer’s disease. Trends Neurosci. 12: 525–530CrossRefGoogle Scholar
  24. Poirier J, Hess M, May PC, Finch CE (1991a) Cloning of hippocampal poly(A+) RNA sequences that increase after entorhinal cortex lesion in adult rat. Mol Brain Res 9: 191–195PubMedCrossRefGoogle Scholar
  25. Poirier J, Hess M, May PC, Finch CE (1991b) Apolipoprotein E and GFAP-RNA in hippocampus during reactive synaptogenesis and terminal proliferation. Mol Brain Res 11: 97–106PubMedCrossRefGoogle Scholar
  26. Poirier J, Baccichet A, Dea D, Gauthier S (1993a) Role of hippocampal cholesterol synthesis and uptake during reactive synaptogenesis in adult rats. Neuroscience 55: 81–90PubMedCrossRefGoogle Scholar
  27. Poirier J, Davignon J, Bouthillier D, Bertrand P, Gauthier S (1993b) Apolipoprotein E and Alzheimer’s disease. Lancet 342: 697–699PubMedCrossRefGoogle Scholar
  28. Poirier J, Aubert I, Bertrand P, Quirion R, Gauthier S, Nalbantoglu J (1994) Apolipoprotein E4 and cholinergic dysfunction in AD: a role for the amyloid/apoE4 complex? In: Giacobini E, Becker RE (eds) Alzheimer’s disease: therapeutic strategies. Birkhäuser, Boston, pp 72– 76Google Scholar
  29. Rail SC, Weisgraber KH, Mahley RW (1982) Abnormal lipoprotein receptor binding activity of the human apoE due to arginine-cysteine interchange at a single site. J Biol Chem 257: 4171– 4178Google Scholar
  30. Saunders AM, Strittmatter WJ, Schmechel D, St George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BA, Gusella JF, McClaclans DR, Alberts MJ, Roses AD (1993) Association of apolipoprotein E allele E4 with late onset familial and sporadic Alzheimer’s disease. Neurology 43: 1467–1472PubMedGoogle Scholar
  31. Schmechel D, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, Roses AD (1993) Increased amyloid -peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer’s disease. Proc Natl Acad Sci USA 90: 9649–9653PubMedCrossRefGoogle Scholar
  32. Soininen H, Kosunen O, Helisalmi S, Mannermaa A, Paljarvi L, Riekkinen O (1995) Severe loss of choline acetyltransferase in the frontal cortex of Alzheimer’s disease patients carrying apolipoprotein E4 allele. Neurosci Lett 187: 79–82PubMedCrossRefGoogle Scholar
  33. Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, Schmechel D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid ß peptide: isoform-specific effect and implication for late onset Alzheimer’s disease. Proc Natl Acad Sci USA 90: 8098–8102PubMedCrossRefGoogle Scholar
  34. Tucek S (1978) Choline acetyltransferase. In: Acetylcholine synthesis in neurons. London, Chapman and Hall Ltd., pp 29–42Google Scholar
  35. Utermann G, Pruin N, Steinmetz A (1979) Apolipoprotein E polymorphism in health and disease. Clin Genet 15: 37–62PubMedCrossRefGoogle Scholar
  36. Zannis VI, Breslow JL (1981) Human VLDL-apoE isoprotein polymorphism is explained by genetic variation and post-translational modifications. Biochemistry 20: 1033–1041PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • J. Poirier
    • 1
  • M.-C. Delisle
  • R. Quirion
  • I. Aubert
  • J. Rocheford
  • I. Rousse
  • S. Gracon
  • M. Farlow
  • S. Gauthier
  1. 1.McGill Centre for Studies in AgingDouglas Hospital Research CentreVerdunCanada

Personalised recommendations