Metabolic Brain Disease

, Volume 9, Issue 1, pp 3–31 | Cite as

The role of β-amyloid peptide in alzheimer's disease

  • Andréa LeBlanc
Review Article


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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abe K., St. George-Hyslop, P., Tanzi, R. and Kogure, K. (1991a). Induction of amyloid precursor protein mRNA after heat shock in cultured human lymphoblastoid cells.Neurosci. Lett. 125: 169–171PubMedGoogle Scholar
  2. Abe K., Tanzi, R. and Kogure, K. (1991b). Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex.Neurosci. Lett. 125: 172–174.PubMedGoogle Scholar
  3. Adroer R., Lopez-Acedo, C., Oliva, R., Hardy, J. and Fidani, L. (1993). A novel silent variant at codon 711 and a variant at codon 708 of the APP sequence detected in Spanish Alzheimer and control cases.Neurosci. Lett. 150: 33–34.PubMedGoogle Scholar
  4. Anderson J., Refolo, L., Wallace, W., Mehta, P., Krishnamurthi, M., Gotlib,et al. (1989) Differential brain expression of the Alzheimer's amyloid precursor protein.EMBO J. 8: 3627–3632.PubMedGoogle Scholar
  5. Anderson J.P., Chen, Y., Kim, K.S. and Robakis, N.K. (1992). An alternative secretase cleavage produces soluble Alzheimer amyloid precursor protein containing a potentially amyloid precursor protein containing a potentially amyloidogenic sequence.J. Neurochem. 59: 2328–2331.PubMedGoogle Scholar
  6. Bahmanyar S., Higgins, G., Goldgaber, D., Lewis, D., Morrison,et al. (1987). Localization of amyloid β-protein messenger RNA in brains from patients with Alzheimer's disease.Science 237: 77–81.PubMedGoogle Scholar
  7. Bakker E., Van Broeckhoven, C., Haan, J., Haan, E., Haan, V., Hul, V., Levy, E., Lieberburg,et al. (1991). DNA diagnosis for Hereditary Cerebral Hemorrhage with amyloidosis (Dutch Type).Am. J. Gen. 49: 518–521.Google Scholar
  8. Balbin M., Abrahamson, M., Gustafson, L., Nilsson, K., Brun, A. and Grubb, A. (1992). A novel mutation in the β-protein coding region of the amyloid β-protein precursor (APP) gene.Hum. Gen. 89: 580–582.Google Scholar
  9. Barrow C. and Zagorski, M. (1991). Solution structures of β-peptide and its constituent fragments: Relation to amyloid deposition.Science 253: 179–182.PubMedGoogle Scholar
  10. Bendotti C., Forloni, G., Morgan, R., O'Hara, B., Oster-Granite, M., Reeves,et al. (1988) Neuroanatomical localization and quantitation of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice.Proc. Natl. Acad. Sci. USA 85: 3628–3632.PubMedGoogle Scholar
  11. Benowitz L., Rodriguez, W., Paskevich, P., Mufson, E., Schenk, D. and Neve, R. (1989). The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects.Exp. Neurol. 106: 237–250.PubMedGoogle Scholar
  12. Bhasin R., Van Nostrand, W., Saitoh, T., Donats, M., barnes, E., Quitschke, W. and Goldgaber, D. (1991). Expression of active secreted forms of human amyloid β-protein precursor by recombinant baculovirus-infected insect cell.Proc. Natl. Acad. Sci. USA 88: 10307–10311.PubMedGoogle Scholar
  13. Boyles J., Zoellner, C., Anderson, L., Kosik, L., Pitas, R., Weisgraber, K., Hui,et al. (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: 1015–1031.PubMedGoogle Scholar
  14. Breen K.C., Bruce, M. and Anderton, B.H. (1991). Beta-Amyloid Precursor Protein Mediates Neuronal Cell-Cell and Cell-Surface Adhesion.J. Neurosci Res 28: 90–100.PubMedGoogle Scholar
  15. Breen K. (1992). APP-collagen interaction is mediated by a heparin bridge mechanism.Mol. Chem. Neuropathol. 16: 109–121.PubMedGoogle Scholar
  16. Burdick D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen,et al. (1992). Assembly and aggregation properties of synthetic Alzheimer's A4/β-amyloid peptide analogs.J. Biol. Chem. 267: 546–554.PubMedGoogle Scholar
  17. Buscoglio J., Gabuzda, D., Matsudaira, P. and Yankner, B. (1993). Generation of β-amyloid in the secretory pathway in neuronal and nonneuronal cells.Proc. Natl. Acad. Sci. USA 90: 2092–2096.PubMedGoogle Scholar
  18. Buxbaum J., Gandy, S., Cicchetti, P., Ehrlich, M., Czernik, A., Fracasso, al. (1990). Processing of Alzheimerβ-/A4 amyloid precursor protein: Modulation by agents that regulate protein phosphorylation.Proc. Natl. Acad. Sci. USA. 87: 6003–6006.PubMedGoogle Scholar
  19. Buxbaum J.D., Oishi, M., Chen, H.I., Pinkas-Kramarski, R., Jaffe, E.A., Gandy, al. (1992). Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer β-/A4 amyloid protein precursor.Proc. Natl. Acad. Sci. USA 89: 10075–1007.PubMedGoogle Scholar
  20. Cai X., Golde, T. and Younkin, S. (1993a). Release of excess amyloid β-protein from a mutant amyloid β-protein precursor.Science 259:514–516.PubMedGoogle Scholar
  21. Cai X.-D., Cheung, T. and Younkin, S. (1993b). Comparison of the Aβ-released from normal amyloid β-protein precursor (β-APP) and from mutant β-APP linked to familial Alzheimer's disease.Soc. Neurosci. Abstr. 19: 430.Google Scholar
  22. Caporaso G., Gandy, S., Buxbaum, J., Ramabhadran, T. and Greengard, P. (1992). Protein phosphorylation regulates secretion of Alzheimer β-/A4 amyloid precursor protein.Proc. Natl. Acad. Sci. USA 89: 3055–3059.PubMedGoogle Scholar
  23. Chen W.-J., Goldstein, J. and Brown, M. (1990). NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor.J. Biol. Chem. 265: 3116–3123.PubMedGoogle Scholar
  24. Chen M. and Yankner, B.A. (1991). An antibody to β-amyloid and the amyloid precursor protein inhibits cell-substratum adhesion in many mammalian cell types.Neurosci. Lett. 125: 223–226.PubMedGoogle Scholar
  25. Chen S.G., Gambetti, P., Xue, R. and LeBlanc, A.C. (1993). Targeting of the amyloid protein precursor to the endoplasmic reticulum: study of APP metabolism.Soc. Neurosci. Abstr. 19: 396Google Scholar
  26. Chong J., Miller, B. and Ghanbari, H. (1990). Detection of amyloid beta protein precursor immunoreactivity in normal and Alzheimer's disease cerebrospinal fluid.Life Sci. 47: 1163–1171.PubMedGoogle Scholar
  27. Citron M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A., Seubert, P.,et al. (1992). Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-amyloid protein production.Nature 360:672–679.PubMedGoogle Scholar
  28. Cohen M., Golde, T., Usiak, M., Younkin, L. and Younkin, S. (1988). In situ hybridization of the nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer disease.Proc. Natl. Acad. Sci. USA 85: 1227–1231.PubMedGoogle Scholar
  29. Cole G., Huynh, T. and Saitoh, T. (1989). Evidence for lysosomal processing of amyloid β-protein precursor in cultured cells.Neurochem. Res. 14: 933–939.PubMedGoogle Scholar
  30. Cole G.M., Galasko, D., Shapiro, P. and Saitoh, T. (1990). Stimulated platelets release amyloid β-protein precursor.Biochem. Biophys. Res. Comm. 170: 288–295.PubMedGoogle Scholar
  31. Cole G., Bell, L., Truong, Q. and Saitoh, T. (1992). An endosomal-lysosomal pathway for degradation of amyloid precursor protein.Ann. NY Acad. Sci. 674: 103–117.PubMedGoogle Scholar
  32. Coon H., Hoff, M., Holik, J., Delisi, L.E., Crowe, T., Freedman, al (1993). C to T nucleotide substitution in codon 713 of amyloid precursor protein gene not found in 86 unrelated schizophrenics from multiplex families.Am. J. Med. Genet. 48: 36–39.PubMedGoogle Scholar
  33. Corder E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, al. 1993. Gene dosage of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families.Science 261: 921–923.PubMedGoogle Scholar
  34. Coyle J.T. and Puttfarcken, P. (1993). Oxidative stress, glutamate, and neurodegenerative disorders.Science 262: 689–695.PubMedGoogle Scholar
  35. Cras P., Kawai, M., Siedlak, S., Mulvihil, P., Gambetti, P., Lowery, al. (1990). Neuronal and microglial involvement in β-amyloid protein deposition in Alzheimer's disease.Am. J. Pathol. 137: 241–246.PubMedGoogle Scholar
  36. Cras P., Kawai, M., Lowery, D., Gonzalez-DeWhitt, P., Greenberg, B. and Perry, G. (1991). Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein.Proc. Natl. Acad. Sci. USA 88: 7552–7556.PubMedGoogle Scholar
  37. De Strooper B., Van Leuven, F. and Van Den Berghe, H. (1992). Alpha 2-macroglobulin and other proteinase inhibitors do not interfere with the secretion of amyloid precursor protein in mouse neuroblastoma cells.Biochim. Biophys. Acta. 1129: 141–143.Google Scholar
  38. De Strooper B., Umans, L., Van Leuvan, F. and Van Den Berghe, H. (1993). Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): Cleavage of APP occurs in a late compartment of the default secretion pathway.J. Cell Biol. 121: 295–304.PubMedGoogle Scholar
  39. Delacourte A. (1990). General and dramatic glial reaction in Alzheimer brains.Neurol 40: 33–37.Google Scholar
  40. deSauvage F. and Octave, J.-N. (1989). A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein.Science 245: 651–653.PubMedGoogle Scholar
  41. Diedrich, J. F., Minnigan, H., Carp, R. I., Whitaker, J.N., Race, R., Frey, W., and Haase, A. T. (1991). Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes.J. Virol. 65: 4759–4768.PubMedGoogle Scholar
  42. Dyrk T., Weidemann, A., Multhaup, G., Salbaum, J., Lemaire, H.G., Kang, al. (1988). Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease.EMBO J. 7: 949–957.PubMedGoogle Scholar
  43. Esch F., Keim, P., Beatties, E., Blacher, R., Culwell, A., Oltersdorf, al. (1990). Cleavage of the amyloid β-peptide during constitutive processing of its precursor.Science 248: 1122–1124PubMedGoogle Scholar
  44. Estus S., Golde, T., Kunishita, T., Blades, D., Lowery, D., Eisen, al. (1992). Potentially amyloidogenic, carboxy-terminal derivatives of the amyloid protein precursor.Science 255: 726–728PubMedGoogle Scholar
  45. Fisher S., Gearhart, J.D. and Ostergranite, M.L. (1991). Expression of the amyloid precursor protein gene in mouse oocytes and embryos.Proc Natl. Acad. Sci. USA 88 1779–1782.PubMedGoogle Scholar
  46. Forloni G., Demicheli, F., Giogi, S., Bendotti, C. and Angeretti, A. (1992). Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1.Mol. Brain Res. 16: 128–134.PubMedGoogle Scholar
  47. Forloni G., Chiesa, R., Smiroldo, S., Verga, L., Salmona, M., Tagliavini, al. (1993) Apoptosis mediated neurotoxicity induced by chronic application of β-amyloid fragment 25–35.Neurorep 4: 523–526.Google Scholar
  48. Frautschy S.A., Baird, A. and Cole, G.M. (1991). Effects of injected Alzheimer β-amyloid cores in rat brain.Proc. Natl. Acad. Sci. USA 88: 8362–8366.PubMedGoogle Scholar
  49. Fukuchi K.-i., Kamino, K., Deeb, S., Smith, A., Dang, T. and Martin, G. (1992). Overexpression of amyloid precursor protein alters its normal processing and is associated with neurotoxicity.Biochem. Biophys. Res. Comm. 182: 165–173.PubMedGoogle Scholar
  50. Gandy S., Bhasin, R., Ramabhadran, T., Koo, E., Price, D., Goldgaber, D. and Greengard, P. (1992). Alzheimer β-A4-amyloid precursor protein: Evidence for putative amyloidogenic fragment.J. Neurochem. 58: 383–386.PubMedGoogle Scholar
  51. Ghiso J., Tostagno, A., Gardella, J.E., Liem, L., Gorevic, P.D. and Frangione, B. (1992). A 109-amino acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, RHDS-, that promotes cell adhesion.Biochem. J. 288: 1053–1059.PubMedGoogle Scholar
  52. Gillespie S.L., Golde, T.E. and Younkin, S.G. (1992). Secretory processing of the Alzheimer amyloid β-A4 protein precursor is increased by protein phosphorylation.Biochem. Biophys. Res.Comm. 187: 1285–1290.PubMedGoogle Scholar
  53. Glenner G. and Wong, C. (1984). Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein.Biochem. Biophys. Res. Commun. 120: 885–890.PubMedGoogle Scholar
  54. Glenner G. (1988). Alzheimer's disease: Its proteins and genes.Cell 52: 307–308.PubMedGoogle Scholar
  55. Goate A., Chartier-Harlin, M., Mullan, M., Brown, J., Crawford, F., Fidani, al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.Nature 349: 704–706.PubMedGoogle Scholar
  56. Goedert M. (1987). Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease.EMBO J. 6: 3627–3632.PubMedGoogle Scholar
  57. Golde T., Estus, S., Usiak, M., Younkin, L. and Younkin, S. (1990). Expression of β-amyloid protein precursor mRNAs: Recognition of a novel alternatively spliced form and quantitation in Alzheimer's disease using PCR.Neuron 4: 253–267.PubMedGoogle Scholar
  58. Golde T., Estus, S., Younkin, L., Selkoe, D. and Younkin, S. (1992). Processing of the amyloid protein precursor to potentially amyloidogenic derivatives.Science 255: 728–730.PubMedGoogle Scholar
  59. Goldgaber D., Lerman, M., McBride, O., Saffiotti, U. and Gajdusek, D. (1987). Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease.Science 235: 887–880.Google Scholar
  60. Goldgaber D., Harris, H., HLA, T., Magiag, T., Donnelly, R., Jacobsen, J., Vitek, M. and Gadjusek, C. (1989). Interleukin 1 regulates synthesis of amyloid β-protein precursor mRNA in human endothelial cells.Proc. Natl. Acad. Sci. USA 86: 7606–7610.PubMedGoogle Scholar
  61. Griffin W.S., Stanley, L.C., Ling, C., White, L., MacLeod, V., Perrot, L.J., White, C.L. and Araoz, C. (1989). Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer's disease.Proc. Natl. Acad. Sci. USA 86: 7611–7615.PubMedGoogle Scholar
  62. Haass C., Hung, A. and Selkoe, D. (1991). Processing of β-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion.J. Neurosci. 1991: 3783–3793.Google Scholar
  63. Haass C., Schlossmacher, M., Hung, A., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, al. (1992a). Amyloid β-peptide is produced by cultured cells during normal metabolism.Nature 359: 322–325.PubMedGoogle Scholar
  64. Haass C., Koo, E., Mellon, A., Hung, A. and Selkoe, D. (1992b). Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments.Nature 357: 500–503.PubMedGoogle Scholar
  65. Haass C., Hung, A., Schlossmacher, M., Teplow, D. and Selkoe, D. (1993). β-amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms.J. Biol. Chem. 268: 3021–3024.PubMedGoogle Scholar
  66. Harter C. and Mellman, I. (1992). Transport of the lysosomal membrane glycoprotein Igp120 (Igp-A) to lysosomes does not require appearance on the plasma membrane.J. Cell. Biol. 117: 311–325.PubMedGoogle Scholar
  67. Hendricks L., Van Duijn, C.M., Cras, P., Cruts, M., Van Hul, W., Van Harskamp, al. (1992). Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β-amyloid precursor protein gene.Nature Gen. 1: 218–221.Google Scholar
  68. Igarashi K., Murai, H. and Asaka, J.-I. (1992). Proteolytic processing of amyloid β-protein precursor (APP) by thrombin.Biochem. Biophys. Res. Comm. 185: 1000–1004.PubMedGoogle Scholar
  69. Itagaki S., McGeer, P., Akiyama, H., Zhu, S. and Selkoe, D. (1989). Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease.J. Neuroimmunol. 24: 173–182.PubMedGoogle Scholar
  70. Izumi R., Yamada, T., Yoshikai, S., Sasaki, H., Hattori, M. and Sasaki, Y. (1992). Positive and negative regulatory elements for the expression of the Alzheimer's disease amyloid precursor-encoding gene in mouse.Gene 112: 189–195.PubMedGoogle Scholar
  71. Jarrett J., Berger, E. and Lansbury, P. (1993). The carboxy terminus of the β-amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheiemr's disease.Biochem. 32: 4693–4697.Google Scholar
  72. Joachim C., Morris, J. and Selkoe, D. (1988). Clinically diagnosed Alzheimer's disease: autopsy results in 150 cases.Ann. Neurol. 24: 50–56.PubMedGoogle Scholar
  73. Johnson S., McNeill, T., Cordell, B. and Finch, C. (1990). Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer's disease.Science 248: 854–857.PubMedGoogle Scholar
  74. Jones C.T., Morris, S., Yates, C.M., Moffoot, A., Sharpe, C., Brock, D.J.H. and St. Clair, D. (1992). Mutation in codon 713 of the β-amyloid precursor protein gene presenting with schizophrenia.Nature Gen. 1: 306–309.Google Scholar
  75. Jones C.T., Morris, S., Moffoot, A., St. Clair, D. and Brock, D.J.H. (1993). Screening Alzheimer's disease patients for mutations in the amyloid precursor protein gene.Molecular and cellular probes 7: 161–165.PubMedGoogle Scholar
  76. Kalaria R., Bhatti, S., Palatinsky, E., Pennington, D., Shelton, E., Chan, al. (1993). Accumulation of the β-amyloid precursor protein at sites of ishemic injury in rat brain.Neurorep. 4: 211–214.Google Scholar
  77. Kang J., Lemaire, H., Unterbeck, A., Salbaum, J., Masters, C., Grzeschik, al. (1987). The precursor of Alzheimer's disease amyloid protein resembles a cell-surface receptor.Nature 325: 733–736.PubMedGoogle Scholar
  78. Kang J. and Müller-Hill, B. (1990). Differential splicing of Alzheimer's disease amyloid A4 precursor RNA in rat tissue: PreA4695 mRNA is predominantly produced in rat and human brain.Biochem. Biophys. Res. Comm. 166: 1192–1200.PubMedGoogle Scholar
  79. Kawarabayashi T., Shoji, M., Harigaya, Y., Yamaguchi, H. and Hirai, S. (1991). Expression of APP in the early stage of brain damage.Brain Res. 563: 334–338.PubMedGoogle Scholar
  80. Kennedy A.M., Newman, S., McCaddon, A., Ba II, J., Roques, P., Mullan, M., Hartdy, al. (1993). Familial Alzheimer's Disease.Brain 116: 309–324.PubMedGoogle Scholar
  81. Kitaguchi N., Takahashi, Y., Tokushima, Y., Shiojiri, S. and Ito, H. (1988). Novel precursor of Alzheimer's Disease amyloid protein shows protease inhibitory activity.Nature 331: 530–532.PubMedGoogle Scholar
  82. Kitaguchi, N., Tokushima, Y., Oishi, K., Takahashi, Y., Shiojiri, S., Nakamura, S.,et al. (1990). Determination of amyloid β-protein precursors harboring active form of proteinase inhibitor domains in cerebrospinal fluid of Alzheimer's disease patients by trypsin-antibody sandwich elisa.Biochem. Biophys. Res. Comm. 166: 1453–1459.PubMedGoogle Scholar
  83. Klier F., Cole, G., Stalleup, W. and Schubert, D. (1990). Amyloid β-protein precursor is associated with extracellular matrix.Brain Res. 515: 336–342.PubMedGoogle Scholar
  84. Knops J., Lieberburg, I. and Sinha, S. (1992). Evidence for a nonsecretory, acidic degradation pathway for amyloid precursor protein in 293 cells.J. Biol. Chem. 267: 16022–16024.PubMedGoogle Scholar
  85. Konig G., Masters, C. and Beyreuther, K. (1990). Retinoic acid induced differentiated neuroblastoma cells show increased expression of the β-A4 amyloid gene of Alzheimer's disease and an altered splicing pattern.FEBS Lett. 269: 305–310.PubMedGoogle Scholar
  86. Konig G., Salbaum, J.M., Wiestler, O., Lang, W., Schmitt, H.P., Masters, C.L. and Beyreuther, K. (1991). Alternative splicing of the beta a4 amyloid gene of Alzheimer's Disease in cortex of control and Alzheimer's Disease patients.Mol. Brain Res. 9: 259–262.PubMedGoogle Scholar
  87. Konig G., Monning, U., Czech, C., Prior, R., Banati, R., Schreiter-Gasser, al. (1992). Identification and differential expression od a novel alternative splice isoform of the β-A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglia cells.J. Biol. Chem. 267: 10804–10809.PubMedGoogle Scholar
  88. Koo E., Sisodia, S., Archer, D., Martin, L., Weidemann, A., Beyreuther, al. (1990). Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport.Proc. Natl. Acad. Sci. USA 87: 1561–1565.PubMedGoogle Scholar
  89. LaFauci G., Lahiri, D., Salton, S. and Robakis, N. (1989). Characterization of the 5'end region and the first two exons of the β-protein precursor gene.Biochem. Biophys. Res. Comm. 159: 297–304.PubMedGoogle Scholar
  90. Lahiri D.K. and Robakis, N.K. (1991). The promoter activity of the gene encoding Alzheimer beta-amyloid precursor protein (APP) is regulated by two blocks of upstream sequences.Mol. Brain Res 9: 253–257.PubMedGoogle Scholar
  91. LeBlanc A., Foldvari, M., Spencer, D., Breckenridge, W., Fenwick, R., Williams, al. (1989). The apolipoprotein A-1 gene is actively expressed in the rapidly myelinating avian peripheral nerve.J. Cell Biol. 109: 1245–1256.PubMedGoogle Scholar
  92. LeBlanc A. and Poduslo, J. (1990). Regulation of apolipoprotein E gene expression after injury of the rat sciatic nerve.J. Neurosci. Res. 25: 162–171.PubMedGoogle Scholar
  93. LeBlanc A., Chen, H., Autilio-Gambetti, L. and Gambetti, P. (1991). Differential APP gene expression in neonatal rat cerebral cortex, meninges and primary astroglial, neuronal and microglial cells.Febs Lett 292: 171–178.PubMedGoogle Scholar
  94. LeBlanc A., Xue, R. and Gambetti, P. (1992a). Translation and processing of amyloid precursor protein are different in rat cortical neurons, astrocytes and microglial cells.Soc. Neurosci. Abst. 18: 149.Google Scholar
  95. LeBlanc A., Kovacs, D., Chen, H., Villare, F., Tykocinski, M., Autilio-Gambetti, L. and Gambetti, P. (1992b). Role of amyloid precursor protein (APP): Study with antisense transfection of human.J. Neurosci. Res. 31: 635–645.PubMedGoogle Scholar
  96. Lemaire H., Salbaum, J., Multhaup, G., Kang, J., Bayney, R., Unterbeck, al. (1989). The PreA4695 precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons.Nucl. Ac. Res. 1989: 517–522.Google Scholar
  97. Levy F., Carman, M., Fernandez-Madrid, I., Power, M., Lieberburg, I., Van Duinen, al. (1990). Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch Type.Science 248: 1124–1126.PubMedGoogle Scholar
  98. Loo D., Copani, A., Pike, C.J., Whittemore, E., Walencewicz, A.J. and Cotman, C.W. (1993). Apoptosis is induced by β-amyloid in cultured central nervous system neurons.Proc. Natl. Acad. Sci. USA 90: 7951–7955.PubMedGoogle Scholar
  99. Lucotte G., Berriche, S. and David, F. (1991). Alzheimer's mutation.Nature 351: 530.Google Scholar
  100. Mahley R. (1988). Apolipoprotein E: Cholesterol transport protein with expanding role in cell biology.Science 240: 622–630.PubMedGoogle Scholar
  101. Malhotra S.K., Shnita, T.K. and Elbrink, J. (1990). Reactive astrocytes — a review.Cytobios 61: 133–160.PubMedGoogle Scholar
  102. Mandybur T. and Chuirazzi, C. (1990). Astrocytes and the plaques of Alzheimer's disease.Neurol. 40: 635–639.Google Scholar
  103. Maruyama K., Kametani, F., Usami, M., Yamao-Harigaya, W. and Tanaka, K. (1991). "Secretase," Alzheimer amyloid protein precursor secreting enzyme is not sequence-specific.Biochem. Biophys. Res. Comm. 179: 1670–1676.PubMedGoogle Scholar
  104. Masters C., Multhaup, G., Simms, G., Pottgiesser, J., Martins, R. and Beyreuther, K. (1985a). Neuronal origin of a cerebral amyloid: Neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.EMBO J. 4: 2757–2763.PubMedGoogle Scholar
  105. Masters C., Simms, G., Weinman, N., Multhaup, G., McDonald, B. and Beyreuther, K. (1985b). Amyloid plaque core protein in Alzheimer disease and Down syndrome.Proc. Natl. Acad. Sci. USA 82: 4245–4249.PubMedGoogle Scholar
  106. Mattson M.P., Cheng, B., Davis, D., Bryant, K., Lieberburg, I. and Rydel, R.E. (1992). β-amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity.J. Neurosci. 12: 376–389.PubMedGoogle Scholar
  107. Mattson M. and Rydel, R. (1992). β-amyloid precursor protein and Alzheimer's disease: the peptide plot thickens.Neurobiol. Aging 13: 617–621.PubMedGoogle Scholar
  108. Mattson M., Cheng, B., Culwell, A., Esch, F., Lieberburg, I. and Rydel, R. (1993). Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein.Neuron 10: 243–254.PubMedGoogle Scholar
  109. Milici A., Salbaum, J. and Beyreuther, K. (1990). Study of the Alzheimer's A4 precursor gene promoter region by genomic sequencing using Taq polymerase.Biochem. Biophys. Res. Comm. 169: 46–50.PubMedGoogle Scholar
  110. Milward E., Papadopoulos, R., Fuller, S., Moir, R., Small, D., Beyreuther, K. and Masters, C. (1992). The amyloid protein precursor of Alzheimer's disease is a mediator of the effects of nerve growth factor on neurite outgrowth.Neuron 9: 129–137PubMedGoogle Scholar
  111. Mita S., Schon, E. and Herbert, J. (1989). Widespread expression of amyloid beta-protein precursor gene in rat brainAm. J. Pathol. 134: 1253–1261.PubMedGoogle Scholar
  112. Miyazaki K., Hasegawa, M., Funahashi, K. and Umeda, M. (1993). A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor.Nature 362: 839–841.PubMedGoogle Scholar
  113. Mori H., Takio, K., Ogawara, M. and Selkoe, D. (1992). Mass spectrometry of purified amyloid β-protein in Alzheimer's disease.J. Biol. Chem. 267: 17082–17086.PubMedGoogle Scholar
  114. Mullan N., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, al. (1992). A pathogenic mutation for the probable Alzheimer's disease in the APP gene at the N-terminus of β-amyloid peptide.Nature Gen. 1: 345–347.Google Scholar
  115. Murrell J., Farlow, M., Ghetti, B. and Benson, M.D. (1991). A mutation in the amyoid precursor protein associated with hereditary Alzheimer's disease.Science 254: 97–99.PubMedGoogle Scholar
  116. Nechiporuk A., Fain, P., Kort, E., Nee, L.E., Frommelt, E., Polinsky, al. (1993). Linkage of Familial Alzheimer Disease to chromosome 14 in two large early-onset pedigrees: Effects of marker allele frequencies on Lod scores.Am. J. Med. Gen. 48: 63–66.Google Scholar
  117. Neruse S., Igarashi, S., Kobayashi, H., Aoki, K., Inuzuka, T., Kanako, al. (1991). Mis-sense mutation Val--Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease.Lancet 337: 978–979.Google Scholar
  118. Neve R., Finch, E. and Dawes, L. (1988). Expression of the Alzheimer amyloid precursor gene transcripts in the human brain.Neuron 1: 669–677.PubMedGoogle Scholar
  119. Neve R., Rogers, J. and Higgins, G. (1990). The Alzheimer amyloid precursor-related transcript lacking the β-A4 sequence is specifically increased in Alzheimer's disease brain.Neuron 5: 329–338.PubMedGoogle Scholar
  120. Neve R., Kammesheidt, A. and Hohmann, C. (1992). Brain transplants of cells expressing the carboxylterminal fragment of the Alzheimer amyloid protein precursor cause specific neuropathology in vivo.Proc. Natl. Acad. Sci. USA 89: 3448–3452.PubMedGoogle Scholar
  121. Ninomiya H., Roch, J., Sundsmo, M., Otero, D. and Saitoh, T. (1993). Amino acid sequence RERMS represents the active domain of amyloid β-A4 protein precursor that promotes fibroblast growth.J. Cell Biol. 121: 879–886.PubMedGoogle Scholar
  122. Nishimoto I., Okamoto, T., Matsuura, Y., Takahashi, S., Okamoto, T., Murayama, Y. and Ogata, E. (1993). Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G0.Nature 362: 75–79.PubMedGoogle Scholar
  123. Nitsch R., Slack, B., Wurtman, R. and Growdon, J. (1992). Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors.Science 258: 304–307.PubMedGoogle Scholar
  124. Nordstedt C., Gandy, S., Alafuzoff, I., Caporaso, G., Iverfeldt, K., Grebb, J., Winblad, B. and Greengard, P. (1991). Alzheimer β-A4 amyloid precursor protein in human brain: Aging associated increases in holoprotein and in a proteolytic fragment.Proc. Natl. Acad. Sci. USA 88: 8910–8914.PubMedGoogle Scholar
  125. Octave J., deSauvage, F. and Maloteaux, J. (1989). Modification of neuronal cell adhesion affects the genetic expression of the A4 amyloid peptide precursor.Brain Res. 486: 369–371.PubMedGoogle Scholar
  126. Ohyagi Y., Takahashi, K., Kamegai, M. and Tabira, T. (1990). Developmental and differential expression of beta amyloid protein precursor mRNAs in mouse brain.Biochem. Biophys. Res. Comm. 167: 54–60.PubMedGoogle Scholar
  127. Oltersdorf T., Ward, P., Henriksson, T., Beattie, E., Neve, R., Lieberburg, I. and Fritz, L. (1990). The Alzheimer's precursor protein: Identification of a stable intermediate in the biosynthetic/ degradative pathway.J. Biol. Chem. 265: 4492–4497.PubMedGoogle Scholar
  128. Oosawa T., Shoji, M., Harigaya, Y., Cheung, T., Shaffer, L., Younkin, L., Younkin, S. and Hirai, S. (1993). The amyloid β-protein in cerebrospinal fluid from Alzheimer's disease patients.Soc. Neurosci. Abstr. 19: 1038.Google Scholar
  129. Otsuka N., Tomonaga, M. and Ikeda, K. (1991). Rapid appearance of β-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury.Brain Res. 568: 335–338.PubMedGoogle Scholar
  130. Palmert M., Golde, T., Cohen, M., Kovacs, D., Tanzi, R., Gusella, al. (1988). Amyloid protein precursor messenger RNAs: Differential expression in Alzheimer's disease.Science 241: 1080–1084.PubMedGoogle Scholar
  131. Palmert M., Podlinsny, M., Witker, D., Oltersdorf, T., Younkin, L., Selkoe, al. (1989a). The β-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid.Proc. Natl. Acad. Sci. USA 86: 6338–6342.PubMedGoogle Scholar
  132. Palmert M., Siedlak, S., Podlinsny, M., Greenberg, B., Shelton, E., Chan, al. (1989b) Soluble derivatives of the β-amyloid protein precursor of Alzheimer's disease are labeled by antisera to the β-amyloid protein.Biochem. Biophys. Res. Comm. 165: 182–188.PubMedGoogle Scholar
  133. Palmert M., Usiak, M., Mayeux, R., Raskind, M., Tourtellotte, W. and Younkin, S. (1990). Soluble derivatives of the β-amyloid protein precursor in cerebrospinal fluid: Alterations in normal aging and in Alzheimer's disease.Neurol. 40: 1028–1034.Google Scholar
  134. Pasternack J.M., Palmert, M.R., Usiak, M., Wang, R., Zurcher-Neely, H., Gonzalez-DeWhitt, al. (1992). Alzheimer's disease and control brain contain soluble derivatives of the amyloid protein precursor that end within the β-amyloid protein region.Biochem. 31: 10936–10940.Google Scholar
  135. Patterson D., Gardiner, K., Kao, F.-T., Tanzi, R., Watkins, P. and Gusella, J. (1988). Mapping of the gene encoding the β-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21.Proc. Natl. Acad. Sci. USA 85: 8266–8270.PubMedGoogle Scholar
  136. Pericakvance M.A., Bebout, J.L., Gaskell, P.C., Yamaoka, L.H., Hung, W.Y., Alberts, al. (1991). Linkage Studies in Familial Alzheimer Disease - Evidence for Chromosome-19 Linkage.Am J Hum Genet 48: 1034–1050.PubMedGoogle Scholar
  137. Pike C.J., Burdick, D., Walencewicz, A.J., Glabe, C.G. and Cotman, C.W. (1993). Neurodegeneration induced by β-amyloid peptides in vitro: The role of peptide assembly state.J. Neurosci. 13: 1676–1687.PubMedGoogle Scholar
  138. Podlisny M.B., Mammen, A.L., Schlossmacher, M.G., Palmert, M.R., Younkin, S.G. and Selkoe, D.J. (1990). Detection of soluble forms of the β-amyloid precursor protein in human plasma.Biochem. Biophys. Res. Comm. 167: 1094–1101.PubMedGoogle Scholar
  139. Podlisny M.B., Stephenson, D.T., Frosch, M.P., Tolan, D.R., Lieberburg, I., Clemens, J.A. and Selkoe, D.J. (1993). Microinjection of synthetic amyloid β-protein in monkey cerebral cortex fails to produce acute neurotoxicity.Am. J. Pathol. 142: 17–24.PubMedGoogle Scholar
  140. Poirier J., Davignon, J., Bouthillier, D., Kogan, S., Bertrand, P. and Gauthier, S. (1993). Apolipoprotein E polymorphism and Alzheimer's disease.Lancet 342: 697–699.PubMedGoogle Scholar
  141. Pollwein P., Masters, C. and Beyreuther, K. (1991). The expression of the amyloid precursor protein (APP) is regulated by the two GC-elements in the promoter.Nucl. Ac. Res. 20: 63–68Google Scholar
  142. Ponte P., DeWhitt-Gonzalez, P., Schilling, J., Miller, J., Hsu, D., Greenberg, al. (1988). A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors.Nature 331: 525–527.PubMedGoogle Scholar
  143. Prelli F., Levy, E., Van Duinen, S., Bots, G., Luyendijk, W. and Frangione, B. (1990). Expression of a normal and variant Alzheiemr's β-protein gene in amyloid of Hereditary Cerebral Hemorrhage, Dutch Type; DNA and protein diagnostic assays.Biochem. Biophys. Res. Comm. 170: 301–307.PubMedGoogle Scholar
  144. Prior R., Monning, U., Schreitergasser, U., Weidemann, A., Blennow, K., Gottfries, al. (1991). Quantitative Changes in the Amyloid beta-A4 Precursor Protein in Alzheimer Cerebrospinal Fluid.Neurosci. Lett. 124: 69–73.PubMedGoogle Scholar
  145. Quitschke W. and Goldgaber, D. (1992). The amyloid β-protein precursor protein promoter: A region essential for transcriptional activity contains a nuclear factor binding domain.J. Biol. Chem. 267: 17362–17368.PubMedGoogle Scholar
  146. Quon, D., Wang, Y., Catalano, R., Scardina, J., Murakami, K. and Cordell, B. (1991). Formation of β-amyloid protein deposits in brains of transgenic mice.Nature 352: 239–241PubMedGoogle Scholar
  147. Ramabhadran T.V., Gandy, S.E., Ghiso, J., Czernik, A.J., Ferris, D., Bhasin, al. (1993). Proteolytic processing of human amyloid β-protein precursor in insect cells.J. Biol. Chem. 268: 2009–2012.PubMedGoogle Scholar
  148. Ramakrishna N., Saikumar, P., Potempska, A., Wisniewski, H.M. and Miller, D.L. (1991). Expression of human Alzheimer amyloid precursor protein in insect cells.Biochem. Biophys. Res. Commun 174: 983–9.PubMedGoogle Scholar
  149. Refolo L., Salton, S., Anderson, J., Mehta, P. and Robakis, N. (1989). Nerve and epidermal growth factors induce the release of the Alzheimer amyloid precursor from PC12 cell cultures.Biochem. Biophys. Res. Comm. 164: 664–670.PubMedGoogle Scholar
  150. Robakis N., Ramakrishna, N., Wolfe, G. and Wisniewski, H. (1987). Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides.Proc. Natl. Acad. Sci. USA 84: 4190–4194.PubMedGoogle Scholar
  151. Roch J., Shapiro, P., Sundsmo, M., Otero, D., Refolo, L., Robakis, N. and Saitoh, T. (1992). Bacterial expression, purification γ, and functional mapping of the amyloid β-A4 protein precursor.J. Cell Biol. 267: 2214–2221.Google Scholar
  152. Rogers J., Cooper, N., Webster, S., Schultz, J., McGeer, P., Styren, al. (1992). Complement activation by β-amyloid in Alzheimer's disease.Proc. Natl. Acad. Sci. USA 89: 10016–10020.PubMedGoogle Scholar
  153. Roher A., Lowenson, J., Clarke, S., Woods, S., Cotter, R., Gowing, E. and Ball, M. (1993). β-amyloid-(1–42) is a major component of cerebrovascular amyloid deposits: Implications for the pathology of Alzheimer's disease.Proc. Natl. Acad. Sci. US 90: 10836–10840.Google Scholar
  154. Saitoh T., Sundsamo, M., Roch, J., Kimura, N., Cole, G., Schubert, al. (1989). Secreted form of amyloid β-protein precursor is involved in the growth regulation of fibroblast.Cell 58: 615–622.PubMedGoogle Scholar
  155. Salbaum J., Weidemann, A., Lemaire, H., Masters, C. and Beyreuther, K. (1988). The promoter of Alzheimer's disease amyloid A4 precursor geneEMBO J. 7: 2207–2813.Google Scholar
  156. Sambamurti K., Shioi, J., Anderson, M.A., Pappolla, M.A. and Robakis, N.K. (1992). Evidence for intracellular cleavage of the Alzheimer's amyloid precursor in PC12 cells.J. Neurosci. Res. 33 319–329.PubMedGoogle Scholar
  157. Schellenberg G.D., Anderson, L., O'dahl, S., Wisjsman, R.M., Sadovnik, A.D., Ball, al. (1991). APP717, APP693, and PRIP gene mutations are rare in Alzheimer disease.Am. Hum. Gen. 49: 511–517.Google Scholar
  158. Schellenberg G.D., Bird, T.D., Wisjsman, R.M., Orr, H.T., Anderson, L., Nemens, al. (1992). Genetic linkage evidence for a Familial Alzheimer's Disease locus on chromosome 14.Science 258: 668–671.PubMedGoogle Scholar
  159. Schubert D., LaCorbiere, M., Saitoh, T. and Cole, G. (1989a). Characterization of an amyloid β-precursor protein that binds heparin and contains tyrosine sulfate.Proc. Natl. Acad. Sci. USA86: 2066–2069.PubMedGoogle Scholar
  160. Schubert D., Jin, L.-W., Saitoh, T. and Cole, G. (1989b). The regulation of amyloid β-protein precursor secretion and its modulatory role in cell adhesion.Neuron 3: 689–694.PubMedGoogle Scholar
  161. Schubert D., Cole, G., Saitoh, T. and Oltersdorf, T. (1989c). Amyloid beta protein precursor is a mitogen.Biochem. Biophys. Res. Comm. 162: 83–88.PubMedGoogle Scholar
  162. Scott J., Parhad, I. and Clark, A. (1991). β-amyloid precursor protein is differentially expressed in axotomized sensory and motor systems.Mol. Brain 10: 315–325.Google Scholar
  163. Seubert P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, al. (1992). Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids.Nature 359: 325–327.PubMedGoogle Scholar
  164. Seubert P., Oltersdorf, T., Lee, M., Barbour, R., Blomquist, C., Davis, al. (1993). Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide.Nature 361: 260–263.PubMedGoogle Scholar
  165. Sherman C. and Higgins, G. (1992). Regulated splicing of the amyloid precursor protein gene during postnatal development of the rat basal forebrain.Dev. Brain Res. 66: 63–69.Google Scholar
  166. Shigematsu K., McGeer, P., Walker, D., Ishii, T. and McGeer, E. (1992). Reactive microglia/ macrophages phagocytose amyloid precursor protein produced by neurons following neural damage.J. Neurosci. Res. 31: 443–453.PubMedGoogle Scholar
  167. Shigematsu K. and McGeer, P. (1992). Accumulation of amyloid precursor protein in damaged neuronal processes and microglia following intracerebral administration of aluminium salts.Brain Res. 593: 117–123.PubMedGoogle Scholar
  168. Shivers B., Hilbich, C., Multhaup, G., Salbaum, M., Beyreuther, K. and Seeburg, P. (1988). Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell-cell contact.EMBO J. 7: 1365–1370.PubMedGoogle Scholar
  169. Shoji M., Golde, T., Ghiso, J., Cheung, T., Estus, S., Shaffer, al. (1992). Production of the Alzheimer amyloid β-protein by normal proteolytic processing.Science 258: 126–129.PubMedGoogle Scholar
  170. Siman R., Card, P., Nelson, R. and Davis, L. (1989). Expression of β-amyloid precursor protein in reactive astrocytes following neuronal damage.Neuron 3: 275–285.PubMedGoogle Scholar
  171. Siman R., Card, P. and Davis, L. (1990). Proteolytic processing of β-amyloid precursor by calpain I.J Neurosci 10: 2400–2411.PubMedGoogle Scholar
  172. Sisodia S., Koo, E., Beyreuther, K., Unterbeck, A. and Price, D. (1990). Evidence that β-amyloid protein in Alzheimer's disease is not derived by normal processing.Science 248: 492–495.PubMedGoogle Scholar
  173. Sisodia S.S. (1992). β-amyloid precursor protein cleavage by a membrane-bound protease.Proc. Natl. Acad. Sci. USA 89: 6075–6079.PubMedGoogle Scholar
  174. Skene P. and Shooter, E. (1983). Denervated sheath cells secrete a new protein after nerve injuryProc. Natl. Acad. Sci. USA 80: 4169–4173.PubMedGoogle Scholar
  175. Smith C., Wion, D. and Brachet, P. (1991). Nerve growth factor-induced neuronal differentiation is asccompanied by differential splicing of β-amyloid precursor mRNAs in the PC12 cell line.Mol. Brain Res. 10: 351–354.PubMedGoogle Scholar
  176. Smith R.P. and Broze, G.J. (1992). Characterization of platelet-releasable forms of β-amyloid precursor proteins: The effect thrombin.Blood 80: 2252–2260.PubMedGoogle Scholar
  177. Smith C.J., Johnson, E.M., Osborn, P., Freeman, R.S., Neveu, I. and Brachet, P. (1993). NGF deprivation and neuronal degeneration trigger altered β-amyloid precursor protein expression in the rat superior cervical ganglia in vivo and in vitro.Mol. Brain Res. 17: 328–334.PubMedGoogle Scholar
  178. St George Hyslop P.H., Haines, J., Farrer, L., Polinsky, R., Van Broeckhoven, C., Goateet al (1990). Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder.Nature 347: 194–197.PubMedGoogle Scholar
  179. Stephenson D., Rash, K. and Clemens, J. (1992). Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat.Brain Res. 593: 128–135.PubMedGoogle Scholar
  180. Strittmatter W.J., Saunders, A.M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G.S. and Roses, A.D. (1993). Apolipoprotein E: High-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.Proc. Natl. Acad. Sci. USA 90: 1977–1981.PubMedGoogle Scholar
  181. Tagawa K., Kunishita, T., Maruyama, K., Yoshikawa, K., Kominami, E., Tsuchiya, al. (1991). Alzheimer's Disease Amyloid beta-Clipping Enzyme (APP Secretase) — Identification, Purification, and Characterization of the Enzyme.Biochem. Biophys. Res. Comm. 177: 377–387.PubMedGoogle Scholar
  182. Tagliavini F., Ghiso, J., Timmers, W., Giaccone, G., Bugiani, O. and Frangione, B. (1990). Coexistence of Alzheimer's amyloid precursor protein and amyloid protein in cerebral vessel walls.Lab. Investigation 62: 761–767.Google Scholar
  183. Takashima A., Noguchi, K., Sato, K., Hoshino, T. and Imahori, K. (1993). Tau protein kinase I is essential for amyloid β-protein-induced neurotoxicity.Proc. Natl. Acad. Sci. USA 90: 7789–7793.PubMedGoogle Scholar
  184. Tamaoka A., Kalaria, R., Lieberburg, I. and Selkoe, D. (1992). Identification of a stable fragment of the Alzheimer amyloid precursor containing the β-protein in brain microvesselsProc. Natl. Acad. Sci. USA 89: 1345–1349.PubMedGoogle Scholar
  185. Tanaka S., Shiojiri, S., Takahashi, Y., Kitaguchi, N., Ito, H., Kameyama, al. (1989). Tissue-specific expression of three types of β-protein precursor mRNA: Enhancement of protease inhibitor-harboring types in Alzheimer's disease brain.Biochem. Biophys. Res. Comm. 165: 1406–1414.PubMedGoogle Scholar
  186. Tanzi R., Gusella, J., Watkins, P., Bruns, G., St.-George-Hyslop, P., Van Keuren, al. (1987a). Amyloid β-protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus.Science 235: 880–884.PubMedGoogle Scholar
  187. Tanzi R., St George-Hyslop, P., Haines, J., Polinsky, R., Nee, et al. (1987b). The genetic defect in Alzheimer's disease is not tightly linked to the amyloid β-protein gene.Nature 329: 156–157.PubMedGoogle Scholar
  188. Tanzi R., McClatchey, A., Lamperti, E., Villa-Komaroff, L., Gusella, J. and RL, N. (1988). Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease.Nature 331: 528–530.PubMedGoogle Scholar
  189. Tanzi R., Vaula, G., Romano, D.M., Mortilla, M., Huang, T.L., Tupler, R.G., Wasco,et al. (1992). Assessment of amyloid β-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases.Am. J. Hum. Gen. 51: 273–282.Google Scholar
  190. Urakami K., Takahashi, K., Saito, H., Okada, A., Nakamura, S., Tanaka, al. (1992). Amyloid β-protein precursors with kunitz-type inhibitor domains and acetyl-cholinesterase in cerebrospinal fluid from patients with dementia of the Alzheimer type.Acta Neurol. Scan. 85: 343–346.Google Scholar
  191. Van Broeckhoven C., Haan, J., Bakker, E., Hardy, J., Van Hul, W., Wehnert, al. (1990). Amyloid β-protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch).Science 248: 1120–1124.PubMedGoogle Scholar
  192. Van Leuven F., Cassiman, J.-J. and Van Der Berghe, H. (1980). Primary amines inhibit recycling of alpha2M receptors in fibroblasts.Cell 20: 37–43.PubMedGoogle Scholar
  193. Van Nostrand W., Schmaier, A., Farrow, J., Cines, D. and Cunningham, D. (1991). Protease nexin-2/amyloid β-protein precursor in blood is a platelet-specific protein.Biochem. Biophys. Res. Comm. 175: 15–21.PubMedGoogle Scholar
  194. Van Nostrand W., Wagner, S., Shankle, R., Farrow, J., Dick, M., Rozemuller, al. (1992). Decreased levels of soluble amyloid β-protein precursor in cerebrospinal fluid of live Alzheimer disease patients.Proc. Natl. Acad. Sci. USA 89: 2551–2555.PubMedGoogle Scholar
  195. Vaula G., Mortilla, M., Tupler, R., Lukiw, W., Tanzi, R., Polinsky, al. (1992). A novel but non-pathogenic mutation in exon 4 of the human amyloid precursor protein (APP) gene.Neurosci. Lett. 144: 46–48.PubMedGoogle Scholar
  196. Wallace W.C., Ahlers, S.T., Gotlib, J., Bragin, V., Sugar, J., Gluck, al. (1993). Amyloid precursor protein in the cerebral cortex is rapidly and persistently induced by loss of subcortical innervation.Proc. Natl. Acad. Sci. USA 90: 8712–8716.PubMedGoogle Scholar
  197. Wang R., Meschia, J., Cotter, R. and Sisodia, S. (1991). Secretion of the β-A4 amyloid precursor protein: Identification of a cleavage site in cultured mammalian cells.J. Biol. Chem. 266: 16960–16964.PubMedGoogle Scholar
  198. Weidemann A., Konig, G., Bunke, D., Fischer, P., Salbaum, J., Masters, al. (1989). Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein.Cell 57: 115–126.PubMedGoogle Scholar
  199. Whitson J., Selkoe, D. and Cotman, C. (1989). Amyloid β-protein enhances the survival of hippocampal neurons in vitro.Science 243: 1488–1490.PubMedGoogle Scholar
  200. Willoughby D., Johnston, S., Pasinetti, G., Tocco, G., Najm, I., Baudry, al. (1992). Amyloid precursor protein mRNA encoding the Kunitz protease inhibitor domain is increased by kainic acid-induced seizures in rat hippocampus.Exp. Neurol. 118: 332–339.PubMedGoogle Scholar
  201. Wisniewski K., Wisniewski, H. and Wen, G. (1985). Occurence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome.Ann. Neurol. 17: 278.PubMedGoogle Scholar
  202. Wisniewski H., Wegiel, J., Wang, M., Kujawa, M. and Lach, B. (1989). Ultrastructural studies of the cells forming amyloid fibers in classical plaques.Can. J. Neurol. Sci. 16: 535–542.PubMedGoogle Scholar
  203. Wisniewski T., Golabek, A., Matsubara, E., Ghiso, J. and Frangione, B. (1993). Apolipo protein E: Binding to soluble Alzheimer's β-amyloid.Biochem. Biophys. Res. Comm. 192: 359–365.PubMedGoogle Scholar
  204. Wong C., Quaranta, V. and Glenner, G. (1985). Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenetically related.Proc. Natl. Acad. Sci. USA 82: 8729–8732.PubMedGoogle Scholar
  205. Yamada T., Sasaki, H., Dohura, K., Goto, I. and Sakaki, Y. (1989). Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer's disease amyloid beta protein precursor.Biochem. Biophys. Res. Comm. 158: 906–912.PubMedGoogle Scholar
  206. Yang F., Jansen, L., Friedrichs, W.E., Buchanan, J.M. and Bowman, B.H. (1993). Il-1ß-decreases expression of amyloid precursor protein gene in human glioma cells.Biochem. Biophys. Res. Comm. 191: 1014–1019.PubMedGoogle Scholar
  207. Yankner B.A., Dawes, L.R., Fisher, S., Villa-Komaroff, L., Oster-Granite, M. and Neve, R.L. (1989). Neurotoxicity of a fragment of the amyloid precursor protein associated with Alzheimer's disease.Science 245: 417–420.PubMedGoogle Scholar
  208. Yankner B.A., Duffy, L.K. and Kirschner, D.A. (1990). Neurotrophic and neurotoxic effects of amyloid β-protein: reversal by tachykinin neuropeptides.Science 250: 279–286.PubMedGoogle Scholar
  209. Yoshikai S., Sasaki, H., Doh-ura, K., Furuya, H. and Sakaki, Y. (1990). Genomic organization of the human amyloid beta-protein precursor gene.Gene 87: 257–263.PubMedGoogle Scholar
  210. Yoshikawa K., Aizawa, T. and Maruyama, K. (1990). Neural differentiation increases expression of Alzheimer amyloid protein precursor gene in murine embryonal carcinoma cells.Biochem. Biophys. Res. Comm. 171: 204–209.PubMedGoogle Scholar
  211. Yoshikawa K., Aizawa, T. and Hayashi, Y. (1992). Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor.Nature 359: 64–67.PubMedGoogle Scholar
  212. Yoshioka K., Miki, T., Katsuya, T., Ogihara, T. and Sakaki, Y. (1991). The 717 Val—Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups.Biochem. Biophys. Res. Comm. 178: 1141–1146.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • Andréa LeBlanc
    • 1
    • 2
  1. 1.Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  2. 2.Bloomfield Center for Research in Aging, Lady Davis Institute for Medical ResearchSir Mortimer B. Davis Jewish General HospitalMontrealCanada

Personalised recommendations