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Monoclonal antibody to β peptide, recognizing amyloid deposits, neuronal cells and lipofuscin pigments in systemic organs

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Summary

A monoclonal antibody (AmT-1) produced against synthetic amyloid β peptide (1–28 residues) was revealed to be reactive with amyloid β peptide blotted on nitrocellulose membrane, but not with that dissolved in sodium dodecyl sulfate and electrophoresed. AmT-1 immunostained senile plaques of typical, primitive and diffuse type, as well as amyloid deposits in cerebral vessels. It also reacted with neuronal and glial cells of normal and Alzheimer's disease (AD) brains. In addition, AmT-1 was also reactive strongly with lipofuscin pigments of adrenal reticular cells, and weakly with those of eccrine glands and liver cells. A rat neural cell line (PC12h) was reactive with AmT-1. By immunoelectron microscopy, a positive reaction was seen in ribosomes along the rough endoplasmic reticulum of nerve cells and PC12h cells. By immunoprecipitation, AmT1 reacted with a band at 36 kDa in the brain homogenates from Ad patients as well as from normal aged subjects. By immunoblotting analysis, AmT1 reacted with a band at 36 kDa in the cytosolic fraction of PC12 cells, and three bands (12–17 kDa) in the lipopigment fraction of the adrenal gland. These findings suggest that the cerebral amyloid deposits contain substance(s) having an epitope common to neuronal cells and lipofuscin pigments. The possible relationship between cerebral amyloid deposits and lipofuscin pigments in systemic organs is discussed.

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References

  1. 1.

    Allsop D, Wong CW, Ikeda A, Landon M, Kidd M, Glenner GG (1988) Immunohistochemical evidence for the derivation of a peptide ligand from the amyloid β-protein precursor of Alzheimer disease. Proc Natl Acad Sci USA 85:2790–2794

  2. 2.

    Bahmanyar S, Higgins GA, Goldgaber D, Lewis DA, Morrison JH, Wilson MC, Shankar SK, Gajdusek DC (1987) Localization of amyloid β protein mRNA in brains from patients with Alzheimer's disease. Science 237:77–80

  3. 3.

    Bancher C, Grundke-Iqbal I, Iqbal K, Kim KS, Wisniewski HM (1989) Immunoreactivity of neuronal lipofuscin with monoclonal antibodies to the amyloid β-protein. Neurobiol Aging 10:125–132

  4. 4.

    Benowitz LI, Rodrigues W, Paskevich P Mufson EJ, Scenk D, Neve RL (1989) The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer disease subjects. Exp Neurol 106:237–250

  5. 5.

    Card JP, Maede RP, Davis LG (1988) Immunocytochemical localization of the precursor protein for β-amyloid in the rat central nervous system. Neuron 1:835–846

  6. 6.

    Catteruccia N, Willingale-Theune J, Bunke D, Prior R, Masters CL, Crisanti A, Beyreuther K (1990) Ultrastructural localization of the putative precursors of the A4 amyloid protein associated with Alzheimer's disease. Am J Pathol 137:19–26

  7. 7.

    Cohen ML, Golde TE, Usiak MF, Youkin LH, Youkin SG (1988) In situ hybridization of nucleus basalis neurons shows increased β amyloid mRNA in Alzheimer's disease. Proc Natl Acad Sci USA 85:1227–1231

  8. 8.

    Cras P, Kawai M, Siedlak S, Mulvihill P, Gambetti P, Lowery D, Gonza'lez-Dewhitt P, Greenberg B, Perry G (1990) Neuronal and microglial involvement in β amyloid protein deposition in Alzheimer's disease. Am J Pathol 137:241–246

  9. 9.

    Glenner GG, Wong CW (1984) Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890

  10. 10.

    Glenner GG, Wong CW (1984) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135

  11. 11.

    Golde TE, Estus S, Usiak M, Younkin LH, Younkin SG (1990) Expression of β amyloid protein precursor mRNA: recognition of a novel alternatively spliced form and quantification in Alzheimer's disease using PCR. Neuron 4:253–267

  12. 12.

    Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC (1987) Characterization and chromosomal localization of a DNA encoding brain amyloid of Alzheimer's disease. Science 235:877–880

  13. 13.

    Grunke-Iqbal I, Iqbal K, Tung Y-C, Kim KS, Wisniewski HM (1989) Amyloid protein and neurofibrillary tangles coexist in the same neuron in Alzheimer disease. Proc Natl Acad Sci USA 86:2853–2857

  14. 14.

    Hatanaka H (1981) Nerve growth factor-mediated stimulation of tyrosine hydroxylase activity in a clonal rat pheochromocytoma cell line. Brain Res 222:225–233

  15. 15.

    Hirokawa K, Utsuyama M, Morrizumi E, Handa S (1986) Analysis of the thymic microenvironment by monoclonal antibodies with special reference to thymic nurse cells. Thymus 8:349–360

  16. 16.

    Ikeda S, Allsop D, Glenner GG (1989) The morphology and distribution of plaque and related deposits in the brains of Alzheimer's disease and control cases: an immunohistochemical study using amyloid β-protein antibody. Lab Invest 60:113–122

  17. 17.

    Joachim CL, Mori H, Selkoe DJ (1989) Amyloid β-protein deposition in tissues other than Alzheimer's disease. Nature 341:226–230

  18. 18.

    Kang J, Lemaire H-G, Untelbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B, (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–735

  19. 19.

    Kawasaki H, Utsuyama H, Takahashi H, Hayashi Y, Kurashima C, Esaki Y, Maruyama M, Hirokawa K (1989) Establishment of a monoclonal antibody against senile plaques and its application for immunohistological and immunoelectron microscopical studies in the brain of the elderly. Acta Neuropathol 79:44–47

  20. 20.

    Kitaguchi T, Wisniewski KE, Maslinski S, Maslinska D, Wisniewski TM, Kim KS (1990) β-protein immunoreactivity in brains of patients with neuronal ceroid lipofuscinosis: ultrastructural and biochemical demonstration. Neurosci Lett 112:155–160

  21. 21.

    Lewis DA, Higgins GA, Young WG, Goldgaber D, Gadjusek DC, Wilson MC, Morrison JH (1988) Distribution of precursor amyloid β protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques. Proc Natl Acad Sci USA 85:1691–1695

  22. 22.

    Mita S, Schon EA, Herbert J (1989) Widespread expression of amyloid β protein precursor gene in rat brain. Am J Pathol 134:1253–1261

  23. 23.

    Masters CL, Multhaup G, Simms G, Pottigiesser J, Martins RN, Beyreuther K (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tanges of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4:2757–2763

  24. 24.

    Masters CL, Simms G, Weinmann NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer's disease and Down's syndrome. Proc Natl Acad Sci USA 82:4245–4249

  25. 25.

    Ogomori K, Kitamoto J, Teteishi Y, Sato M, SueTsugu M, Abe M (1989) β-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease. Am J Pathol 134:243–250

  26. 26.

    Palmer DN, Barns G, Husbands DR, Jolly RD (1986) Ceroid lipofuscinosis in sheep. II. The major component of the lipopigment in liver, kidney, pancreas and brain is low molecular weight protein. J Biol Chem 261:1773–1777

  27. 27.

    Palmert MR, Berman-Podlisny M, Whitker DS, Oltersdorf Y, Youkin LH, Selkoe DJ, Youkins SG (1988) Antisera to an amino-terminal peptide detect the amyloid protein precursor of Alzheimer's disease and recognize senile plaques. Biochem Biophys Res Commun 156:432–437

  28. 28.

    Robakis NK, Ramakrishna N, Wolfe G, Wisniewski HM (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

  29. 29.

    Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, Oltersdorf T (1988) β amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kDa membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci USA 85:7341–7345

  30. 30.

    Shivers BD, Hilbich C, Multhaup G, Salbaum M, Beyreuther, Seeburg PH (1988) Alzheimer's disease amyloidgenic glyco-protein: expression pattern in rat brain suggests a role in cell contact. EMBO J 7:1365–1370

  31. 31.

    Siman R, Card P, Nelson RB, Davis LG (1989) Expression of β-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron 3:275–285

  32. 32.

    Stern RA, Otvos L, Trojanowski JQ, Lee VM-Y (1989) Monoclonal antibodies to a synthetic peptide homologous with the first 28 amino acids of Alzheimer's disease β-protein recognize amyloid and diverse glial and neuronal cell types in the central nervous system. Am J Pathol 135:973–978

  33. 33.

    Takahashi H, Kurashima C, Utsuyama M, Hirokawa K (1990) Immunohistological study of senile brains by using a monoclonal antibody recognizing β amyloid precursor protein: significance of granular deposits in relation with senile plaques. Acta Neuropathol 80:260–265

  34. 34.

    Tanzi RE, Gusella JF, Watkins PC, Bruns GAP, St George-Hyslop P, Vankeuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (1987) Amyloid β protein gene: cDNa, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235:880–883

  35. 35.

    Tate-Ostroff B, Majocha RE, Marota CA (1989) Identification of cellular and extracellular sites of amyloid precursor protein extracytoplasmic domain in normal and Alzheimer disease brains. Proc Natl Acad Sci USA 86:745–749

  36. 36.

    Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354

  37. 37.

    Wisniewski KE, Kida E, Gordon-Majszak W, Saitoh T (1990) Altered amyloid β-protein precursor processing in brains of patients with neuronal ceroid lipofuscinosis. Neurosci Lett 120:94–96

  38. 38.

    Wisniewski KE, Maslinska D, Kitaguchi T, Kim KS, Goebel HH, Haltia M (1990) Topographic heterogeneity of amyloid β-protein epitopes in brains with various forms of neuronal ceroid lipofuscinoses suggesting defective processing of amyloid precursor protein. Acta Neuropathol 80:26–34

  39. 39.

    Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Ihara Y (1988) A variety of cerebral amyloid deposits in the brains of the Alzheimer-type dementia demonstrated by β protein immunostaining. Acta Neuropathol 76:541–549

  40. 40.

    Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Harigaya Y (1988) Diffuse type of senile plaques in the brains of Alzheimer-type dementia. Acta Neuropathol 77:113–119

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Takahashi, H., Utsuyama, M., Kurashima, C. et al. Monoclonal antibody to β peptide, recognizing amyloid deposits, neuronal cells and lipofuscin pigments in systemic organs. Acta Neuropathol 85, 159–166 (1993). https://doi.org/10.1007/BF00227763

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Key words

  • Monoclonal antibody
  • Amyloid β peptide
  • Senile plaques
  • Nerve cells
  • Lipofuscin