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2000 | 47 | 3 | 725-733
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Alzheimer's disease: Its origin at the membrane, evidence and questions.

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Numerous results on membrane lipid composition from different regions of autopsied Alzheimer's disease brains in comparison with corresponding fractions isolated from control brains revealed significant differences in serine- and ethanolamine-containing glycerophospholipid as well as in glycosphingolipid content. Changes in membrane lipid composition are frequently accompanied by alterations in membrane fluidity, hydrophobic mismatch, lipid signaling pathways, transient formation and disappearance of lipid microdomains, changes in membrane permeability to cations and variations of other membrane properties. In this review we focus on possible implications of altered membrane composition on β-amyloid precursor protein (APP) and on proteolysis of APP leading eventually to the formation of neurotoxic β-amyloid (Aβ) peptides, the major proteinaceous component of extracellular senile plaques, directly involved in Alzheimer's disease pathogenesis.
Physical description
  • Laboratoire de Physico-Chimie Biologique, Université Claude Bernard-Lyon 1, UFR de Chimie-Biochimie, CNRS UMR 5013, F-69622 Villeurbanne, France
  • Department of Cellular Biochemistry, M. Nencki Institute of Experimental Biology, L. Pasteura 3, 02-093 Warszawa, Poland
  • 1. Selkoe, D.J. (1994) Cell biology of the amyloid β-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell Biol. 10, 373-403.
  • 2. Van Broeckhoven, C.L. (1995) Molecular genetics of Alzheimer disease: Identification of genes and gene mutations. Eur. Neurol. 35, 8-19.
  • 3. Small, D.H. & McLean, C.A. (1999) Alzheimer's disease and the amyloid β protein: What is the role of amyloid? J. Neurochem. 73, 443-449.
  • 4. Storey, E., Katz, M., Brickman, Y., Beyreuther, K. & Masters, C.L. (1999) Amyloid precursor protein of Alzheimer's disease: Evidence for a stable, full-length, trans-membrane pool in primary neuronal cultures. Eur. J. Neurosci. 11, 1779-1788.
  • 5. Hardy, J. (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 20, 154-159.
  • 6. Flint Beal, M.F. (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 23, 298-304.
  • 7. Auld, D.S., Kar, S. & Quirion, R. (1998) β-Amyloid peptides as direct cholinergic neuromodulators: A missing link? Trends Neurosci. 21, 43-49.
  • 8. Neve, R.L. & Robakis, N.K. (1998) Alzheimer's disease: A re-examination of the amyloid hypothesis. Trends Neurosci. 21, 15-19.
  • 9. Racchi, M. & Govoni, S. (1999) Rationalizing a pharmacological intervention on the amyloid precursor protein metabolism. Trends Pharmacol. Sci. 20, 418-423.
  • 10. Prasad, M.R., Lovell, M.A., Yatin, M., Dhillon, H. & Markesbery, W.R. (1998) Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem. Res. 23, 81-88.
  • 11. Wells, K., Farookui, A.A., Liss, L. & Horrocks, L.A. (1995) Neural membrane phospholipids in Alzheimer disease. Neurochem. Res. 20, 1329-1333.
  • 12. Ginsberg, L., Xuereb, J.H. & Gershfeld, N.L. (1998) Membrane instability, plasmalogen content, and Alzheimer's disease. J. Neurochem. 70, 2533-2538.
  • 13. Killian, J.A. (1998) Hydrophobic mismatch between proteins and lipids in membranes. Biochim. Biophys. Acta 1376, 401-415.
  • 14. Sinha, S. & Lieberburg, I. (1999) Cellular mechanism of β-amyloid production and secretion. Proc. Natl. Acad. Sci. U.S.A. 96, 11049- 11053.
  • 15. de La Fournière-Bessueille, L., Grange, D. & Buchet, R. (1997) Purification and spectroscopic characterization of β-amyloid precursor protein from porcine brains. Eur. J. Biochem. 250, 705-711.
  • 16. Tomita, S., Kirino, Y. & Suzuki, T. (1998) Cleavage of Alzheimer's amyloid precursor protein (APP) by secretases occurs after O-glycosylation of APP in the protein secretory pathway. Identification of intracellular compartments in which APP cleavage occurs without using toxic agents that interfere with protein metabolism. J. Biol. Chem. 273, 6277-6284.
  • 17. Parvathy, S., Hussain, I., Karran, E.H., Turner, A.J. & Hooper, N.M. (1999) Cleavage of Alzheimer's amyloid precursor protein by α-secretase occurs at the surface of neuronal cells. Biochemistry 38, 9728-9734.
  • 18. Kosik, K.S. (1999) A notable cleavage: Winding up with β-amyloid. Proc. Natl. Acad. Sci. U.S.A. 96, 2574-2576.
  • 19. Tezapsidis, N., Li, H.C., Ripellino, J.A., Efthimiopoulos, S., Vassilacopoulou, D., Sambamurti, K., Toneff, T., Yasothornsrikul, S., Hook, V.Y.H. & Robakis, N.K. (1998) Release of nontransmembrane full-length Alzheimer's precursor protein from the lumenal surface of chromaffin granule membranes. Biochemistry 37, 1274-1282.
  • 20. Wolfe, M.S., De Los Angeles, J., Miller, D.D., Xia, W. & Selkoe, D.J. (1999) Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's diseases. Biochemistry 38, 11223- 11230.
  • 21. Lichtenthaler, S.F., Ida, N., Multhaup, G., Masters, C.L. & Beyreuther, K. (1997) Mutations in the transmembrane domain of APP altering γ-secretase specificity. Biochemistry 36, 15396-15403.
  • 22. Parvathy, S., Hussain, I., Karran, E.H., Turner, A.J. & Hooper, N.M. (1998) Alzheimer's amyloid precursor protein α-secretase is inhibited by hydroxamic acid-based zinc metalloprotease inhibitors: Similarities to the angiotensin converting enzyme secretase. Biochemistry 37, 1680-1685.
  • 23. Vassar, R., Bennett, B.D., Babu-Khan, S., Kahn, S., Mendlaz, E.A., Denis, P., Teplow, D.B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., Jarosinski, M.A., Biere, A.L., Curran, E., Burgess, T., Louis, J.C., Collins, F., Treanor, J., Rogers, G. & Citron, M. (1999) β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741.
  • 24. Sinha, S., Anderson, J.P., Barbour, R., Basi, G.S., Caccavello, R., Davis, D., Doan, M., Dovey, H.F., Frigon, N., Hong, J., Jacobson-Croak, K., Jewett, N., Keim, P., Knops, J., Lieberburg, I., Power, M., Tan, H., Tatsuno, G., Tung, J., Schenk, D., Seubert, P., Suomensaari, S.M., Wang, S., Walker, D., Zhao, J., McConlogue, L. & Varghese, J. (1999) Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 402, 537-540.
  • 25. Yan, R., Bienkowski, M.J., Shuck, M.E., Miao, H., Tory, M.C., Pauley, A.M., Brashler, J.R., Stratman, N.C., Mathews, W.R., Buhl, A.E., Carter, D.B., Tomaselli, A.G., Parodi, L.A., Heinrikson, R.L. & Gurney, M.E. (1999) Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity Nature 402, 533-537.
  • 26. Hussain, I., Powell, D., Howlett, D.R., Tew, D.G., Meek, T.D., Chapman, C., Gloger, I.S., Murphy, K.E., Southan, C.D., Ryan, D.M., Smith, T.S., Simmons, D.L., Walsh, F.S., Dingwall, C. & Christie, G. (1999) Identification of a novel aspartic protease (Asp 2) as a β-secretase. Mol. Cell Neurosci. 14, 419-427.
  • 27. Lin, X., Koelsch, G., Wu, S., Downs, D., Dashti, A. & Tang, J. (2000) Human aspartic protease memapsin 2 cleaves the β-secretase site of β-amyloid precursor protein. Proc. Natl. Acad. Sci. U.S.A. 97, 1456-1460.
  • 28. Wolfe, M.S., Xia, W., Ostaszewski, B.L., Diehl, T.S., Kimberly, W.T. & Selkoe, D.J. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature 398, 513-517.
  • 29. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J.S., Schroeter, E.H., Schrijvers, V., Wolfe, M.S., Ray, W.J., Goate, A. & Kopan, R. (1999) A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522.
  • 30. Struhl, G. & Greenwald, I. (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398, 522-525.
  • 31. Ye, Y., Lukinova, N. & Fortini, M.E. (1999) Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants. Nature 398, 525-529.
  • 32. Li, Y.M., Ksu, M., Lai, M.T., Huang, Q., Castro, J.L., DiMuzio-Mower, J., Harrison, T., Lellis, C., Nadin, A., Neduvelil, J.G., Register, R.B., Sardana, M.K., Shearman, M.S., Smith, A.L., Shi, X.P., Yin, K.C., Shafer, J.A. & Gardell, S.J. (2000) Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1. Nature 405, 689- 694.
  • 33. Parkin, E.T., Hussain, I., Turner, A.J. & Hoper, N.M. (1997) The amyloid precursor protein is not enriched in caveolae-like, detergent-insoluble membrane microdomains. J. Neurochem. 69, 2179-2188.
  • 34. Hayashi, H., Mizuno, T., Michikawa, M., Haass, C. & Yanagisawa, K. (2000) Amyloid precursor protein in unique cholesterol-rich microdomains different from caveolae-like domains. Biochim. Biophys. Acta 1483, 81-90.
  • 35. Parkin, E.T., Turner, A.J. & Hoper, N.M. (1999) Amyloid precursor protein, although partially detergent-insoluble in mouse cerebral cortex, behaves as an atypical lipid raft protein. Biochem. J. 344, 23-30.
  • 36. Simons, M., Keller, P., De Strooper, B., Beyreuther, K., Dotti, C.G. & Simons, K. (1998) Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons. Proc. Natl. Acad. Sci. U.S.A. 95, 6460-6464.
  • 37. Ikezu, T., Trapp, B.D., Song, K.S., Schlegel, A., Lisanti, M.P. & Okamoto, T. (1998) Caveolae, plasma membrane microdomains for α-secretase-mediated processing of the amyloid precursor protein. J. Biol. Chem. 273, 10485-10495.
  • 38. Morishima-Kawashima, M. & Ihara, Y. (1998) The presence of amyloid β-protein in the detergent-insoluble membrane compartment of human neuroblastoma cells. Biochemistry 37, 15247-15253.
  • 39. Parkin, E.P., Hussain, I., Karran, E.H., Turner, A.J. & Hooper, N.M. (1999) Characterization of detergent-insoluble complexes containing the familial Alzheimer's disease-associated presenilins. J. Neurochem. 72, 1534- 1543.
  • 40. Pike, C.J., Burdick, D., Walencewicz, A.J., Glabe, C.G. & Cotman, C.W. (1993) Neurodegeneration induced by β-amyloid peptides in vitro: The role of peptide assembly state. J. Neurosci. 13, 1676-1687.
  • 41. Simmons, L.K., May, P.C., Tomaselli, K.J., Rydel, R.E., Fuson, K.S., Brigham, E.F., Wright, S., Lieberburg, I., Becker, G.W., Brems, D.N. & Li, W.Y. (1993) Secondary structure of amyloid β peptide correlates with neurotoxic activity in vitro. Mol. Pharmacol. 45, 373-379.
  • 42. Buchet, R., Tavitian, E., Ristig, D., Svoboda, R., Stauss, U., Gremlich, H.U., de La Fournière, L., Staufenbiel, M., Frey, P. & Lowe, D.A. (1996) Conformations of synthetic β peptides in solid state and in aqueous solution: Relation to toxicity in PC12 cells. Biochim. Biophys. Acta 1315, 40-46.
  • 43. Hirakura, Y., Satoh, Y., Hirashima, N., Suzuki, T., Kagan, B.L. & Kirino, Y. (1998) Membrane perturbation by neurotoxic Alzheimer amyloid fragment β25-35 requires aggregation and β-sheet formation. Biochem. Mol. Biol. Int. 46, 787-794.
  • 44. McLaurin, J., Franklin, T., Chakrabartty, A. & Fraser, P.E. (1998) Phosphatidylinositol and inositol involvement in Alzheimer amyloid-β fibril growth and arrest. J. Mol. Biol. 278, 183-194.
  • 45. Choo-Smith, L.P., Garzon-Rodriguez, W., Glabe, C.G. & Surewicz, W.K. (1997) Acceleration of amyloid fibril formation by specific binding of Aβ-(1-40) peptide to ganglioside-containing membrane vesicles. J. Biol. Chem. 272, 22987-22990.
  • 46. Matsuzaki, K. & Horikiri, C. (1999) Interactions of amyloid β-peptide (1-40) with ganglioside-containing membranes. Biochemistry 38, 4137-4142.
  • 47. del Mar Martínez-Senac, M., Villalaín, J. & Gómez-Fernández, J.C. (1999) Structure of the Alzheimer β-amyloid peptide (25-35) and its interaction with negatively charged phospholipid vesicles. Eur. J. Biochem. 265, 744-753.
  • 48. Arispe, M., Rojas, E. & Pollard, H.B. (1993) Alzheimer disease amyloid β protein forms calcium channels in bilayer membranes: Blockade by tromethamine and aluminum. Proc. Natl. Acad. Sci. U.S.A. 90, 567-571.
  • 49. Lin, H., Zhu, Y.J. & Lal, R. (1999) Amyloid β protein (1-40) forms calcium-permeable, Zn2+-sensitive channels in reconstituted lipid vesicles. Biochemistry 38, 11189-11196.
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