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Inflammatory Markers in Chronic Neurodegenerative Disorders with Emphasis on Alzheimer’s Disease

  • Chapter
Neuroinflammation

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

The concept of the existence of a population of brain resident phagocytic cells was first presented in the early part of the century by Rio-Hortega, who identified a distinct population of ramified cells, now considered to be resting microglia, using a silver carbonate staining method (1). These findings were confirmed by Penfield (2) and Kershman (3) Although these findings are over 50 years old, it has been during the last decade that major progress in microglial studies has been made, and the involvement of these cells in various neurodegenerative diseases has become apparent. The main reason for the progress in these discoveries has been the availability of immunological and molecular tools, developed by immunologists for their studies on peripheral immune system cells, and their application by neuroscientists to study human brain diseases. In just over 20 years since Kohler and Milstein developed the methodology for producing monoclonal antibodies (MAb) (4), a large number of reagents for studying the protein markers expressed by macrophages have become available. Although a number of microglia studies were (and still are) carried out using lectin histochemistry, enzyme histochemistry, and other techniques(5), it has been through the use of MAb to macrophage markers that the strongest evidence that brain-resident microglia represent a population of cells of monocytic origin has been obtained (6) Some researchers today still dispute this conclusion and believe microglia are derived from cells of neuroectodermal origin (7). Evidence from animal studies appears to indicate that the developing brain becomes populated with monocytic cells with the role of removing the cellular debris that arises during synaptic remodeling (6) These cells then remain resident in the brain, developing the ramified morphology characteristic of resting (unactivated) microglia.

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References

  1. del Rio-Hortega, P. (1919) El “tercer elemento” de centros nervisos: Poder fagocitario y movilidad de la microglia.Biol. Soc. Exp. Bio. Ano 9, 154–166.

    Google Scholar 

  2. Penfield, W. (1932) Neuroglia and microglia. The interstitial tissue of the central nervous system, inSpecial cytology, 2nd ed., vol III ( Cowdry, E. V., ed.), Hoeber, New York, Section XXXI, pp. 1445–1482.

    Google Scholar 

  3. Kershman, J. (1939) Genesis of microglia in the human brain.Arch. Neurol. Psychiatry (Chicago) 41, 24–50.

    Article  Google Scholar 

  4. Kohler, G. and Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity.Nature 256, 495–497.

    Article  PubMed  CAS  Google Scholar 

  5. Ling, E. A., Penney, D., and Leblond, C. P. (1980) Use of carbon labelling to demonstrate the role of blood monocytes as precursors of the amebod cellls in the corpus callosuum of postnatal rats.J. Comp. Neurol 193, 631–657.

    Article  PubMed  CAS  Google Scholar 

  6. Perry, V. H., Hume, D. A., and Gordon, S. (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain.Neuroscience 15, 313–326.

    Article  PubMed  CAS  Google Scholar 

  7. Hao, C., Richardson, A., and Fedoroff, S. (1991) Macrophage-like cells originate from neuroepithelium in culture: characterization and properties of the macrophage-like cells.Int. J. Del). Neurosci 9, 1–14.

    Article  CAS  Google Scholar 

  8. Esiri, M. M. and Booss, J. (1984) Comparison of methods to identify microglial cells and macrophages in the human central nervous system.J. Clin. Pathol 150, 150–164.

    Article  Google Scholar 

  9. McGeer, P.L., Itagaki, S., Tago, S., and McGeer, E. G. (1987) Reactive microglia in patients with senile dementia of the Alzheimer’s type are positive for the histocompatibility glycoprotein HLA-DR.Neurosci. Lett 79 (8), 1285–1291.

    Google Scholar 

  10. Rogers, J., Luber, N. J., Styren, S. D., and Civin, W. H. (1988) Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease.Neurobiol. Aging 9 (4), 339–349.

    Article  PubMed  CAS  Google Scholar 

  11. Haga, S., Akai, K., and Ishii, T. (1989) Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody.Acta Neuropathol.77, 569–575.

    Article  PubMed  CAS  Google Scholar 

  12. Perlmutter, L., Barron, E., and Chui, H. C. (1990) Morphologic association between microglia and senile plaque amyloid in Alzheimer’s disease.Neurosci. Lett 119, 32–36.

    Article  PubMed  CAS  Google Scholar 

  13. Glenner, G. G. and Wong, C. W. (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein.Biochem. Biophys. Res. Commun 120 (3), 885–890.

    Article  PubMed  CAS  Google Scholar 

  14. Masters, C. L., Multhaup, G., Simms, G., Pottgiesser, J., Martins, R. N., and Beyreuther, K. (1985) 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 (11), 2757–2763.

    PubMed  CAS  Google Scholar 

  15. Tanzi, R. E., Gusella, J. F., and Watkins, P. C., et al. (1987) Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus.Science 235 (4791), 880–884.

    Article  PubMed  CAS  Google Scholar 

  16. Kang, J., Lemaire, H. G., and Unterbeck, A., et al. (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor.Nature 325 (6106), 733–736.

    Article  PubMed  CAS  Google Scholar 

  17. Goldgaber, D., Lerman, M. I., McBride, O.W., Saffiotti, U., and Gajdusek, D. C. (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease.Science 235 (4791), 877–880.

    Article  PubMed  CAS  Google Scholar 

  18. Banati, R. B., Gehrmann, J., Schubert, P., and Kreutzberg, G. W. (1993) Cytotoxicity of microglia [Review].Glia 7 (1), 111–113.

    Article  PubMed  CAS  Google Scholar 

  19. Banati, R. B. and Graeber, M. B. (1994) Surveillance, intervention and cytotoxicity: is there a protective role of microglia? Dev.Neurosci.16, 114–127.

    CAS  Google Scholar 

  20. McGeer, P. L., Itagaki, S., and McGeer, E. G. (1988) Expression of the histocompatibility glycoprotein HLA-DR in neurological disease.Acta Neuropathol.76 (6), 550–557.

    Article  PubMed  CAS  Google Scholar 

  21. Luber-Narod, J. and Rogers, J. (1988) Immune system associated antigens expressed by cells of the human nervous system.Neurosci. Lett 94 (1–2), 17–22.

    Article  PubMed  CAS  Google Scholar 

  22. Tooyama, I., Kimura, H., Akiyama, H., and McGeer, P. L. (1990) Reactive micro-glia express class I and class II major histocompatibility complex antigens in Alzheimer’s disease.Brain Res.523 (2), 273–280.

    Article  PubMed  CAS  Google Scholar 

  23. Akiyama, H. and McGeer, P. L. (1990) Brain microglia constitutively express beta-2 integrins.J. Neuroimmunol 30 (1), 81–93.

    Article  PubMed  CAS  Google Scholar 

  24. Eikelenboom,P.,Zhan, S. S., and Kamphorst, W., et al. (1994) Cellular and substrate adhesion molecules (integrins) and their ligands in cerebral amyloid plaques in Alzheimer’s disease.Virchows Arch. 424(4),421–427.

    Google Scholar 

  25. Peress, N. S., Fleit, H. B., Perillo, E., Kuljis, R., and Pezzullo, C. (1993) Identification of Fc gamma RI, II and III on normal human brain ramified microglia and on microglia in senile plaques in Alzheimer’s disease.J. Neuroimmunol 48 (1), 71–79.

    Article  PubMed  CAS  Google Scholar 

  26. Matsuo, A., Walker, D. G., Terai, K., and McGeer, P. L. (1996) Expression of CD43 by microglia and its downregulation in Alzheimer’s disease.J. Neuroimmunol 71, 81–86.

    Article  PubMed  CAS  Google Scholar 

  27. Masliah, E., Mallory, M., and Hansen L., et al. (1991) Immunoreactivity of CD45, a protein phosphotyrosine phosphatase, in disease.Acta Neuropathol.83(1), 12–20. 30.

    Google Scholar 

  28. McGeer, P. L., Kawamata, T., Walker, D. G., Akiyama, H., Tooyama,I.,and McGeer, E. G. (1993) Microglia in degenerative neurological disease [Review].Glia 7(1),84–92.

    Google Scholar 

  29. Akiyama, H., Ikeda, K., Katoh, M., McGeer, E. G., and McGeer, P. L. (1994) Expression ofMRP14, 27E10, interferon-alpha and leukocyte common antigen by reactive microglia in postmortem human brain tissue.J. Neuroimmunol 50 (2), 195–201.

    Article  PubMed  CAS  Google Scholar 

  30. Akiyama, H., Kawamata, T., Dedhar, S., and McGeer, P. L. (1991) Immunohistochemical localization of vitronectin, its receptor and beta-3 integrin in Alzheimer brain tissue.J. Neuroimmunol 32 (1), 19–28.

    Article  PubMed  CAS  Google Scholar 

  31. Akiyama, H., Kawamata, T., Yamada, T., Tooyama,I.,Ishii, T., and McGeer, P. L. (1993) Expression of intercellular adhesion molecule (ICAM)-1 by a subset of astrocytes in Alzheimer disease and some other degenerative neurological disorders.Acta Neuropathol. 85(6),628–634.

    Google Scholar 

  32. Verbeek, M. M., Otte-Holler, I., Westphal, J. R., Wesseling, P., Ruiter, D. J., and de Waal, R. M. (1994) Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer’s disease.Am. J. Pathol 144 (1), 104–116.

    PubMed  CAS  Google Scholar 

  33. Verbeek, M. M., Otte-Holler, I., and Wesseling, P., et al. (1995) A lysosomal marker for activated microglial cells involved in Alzheimer classic senile plaques.Acta Neuropathol.90, 493–503.

    Article  PubMed  CAS  Google Scholar 

  34. Griffin, W. S., Stanley, L. C., Ling, C., White, L., and MacLeod, V., et al. (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.Proc. Natl. Acad. Sci. USA 86, 6611–6615.

    Google Scholar 

  35. Griffin, W. S., Sheng, J. G., Roberts, G. W., and Mrak, R. E. (1995) Interleukin-1 expression in different plaque types in Alzheimer’s disease: significance in plaque evolution.J. Neuropathol. Exp. Neurol 54 (2), 276–281.

    Article  PubMed  CAS  Google Scholar 

  36. Sheng, J. G., Mrak, R. E., and Griffin, W. S. T. (1995) Microglial interleukin-la expression in brain regions in Alzheimer’s disease: correlation with neuritic plaque distribution.Neuropathol. Appl. Neurobiol 21, 290–301.

    Article  PubMed  CAS  Google Scholar 

  37. Dickson, D. W., Lee, S. C., Mattiace, L. A., Yen, S. H., and Brosnan, C. (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer’s disease [Review].Glia 7 (1), 75–83.

    Article  PubMed  CAS  Google Scholar 

  38. Peress, N. S. and Perillo E. (1995) Differential expression of TGF-131, 2 and 3 isotypes in Alzheimer’s disease: a comparative immunohistochemical study with cerebral infarction, aged human and mouse control brains.J. Neuropathol. Exp. Neurol 54 (6), 802–811.

    Article  PubMed  CAS  Google Scholar 

  39. Yamada, T., Yoshiyama, Y., Sato, H., Seiki, M., Shinagawa, A., and Takahashi, M. (1995) White matter microglia produce membrane type matrix metalloprotease, an activator of gelatinase A, in human brain tissue.Acta Neuropathol.90 (5), 421–424.

    Article  PubMed  CAS  Google Scholar 

  40. Akiyama, H., Nishimura, T., Kondo, H., Ikeda, K., Hayashi, Y., and McGeer, P. L. (1994) Expression of the receptor for macrophage colony stimulating factor by brain microglia and its upregulation in brains of patients with Alzheimer’s disease and amyotrophic lateral sclerosis.Brain Res.639 (1), 171–174.

    Article  PubMed  CAS  Google Scholar 

  41. Yamada, T., Horisberger, M. A., Kawaguchi, N., Moroo, I., and Toyoda, T. (1994) Immunohistochemistry using antibodies to alpha-interferon and its induced protein, MxA, in Alzheimer’s and Parkinson’s disease brain tissues.Neurosci. Lett.181(1–2), 61–64.

    Google Scholar 

  42. Yamada, T. and Yamanaka, I. (1995) Microglial localization of a-interferon receptor.Neurosci. Lett 189, 73–76.

    Article  PubMed  CAS  Google Scholar 

  43. Jefferies, W. A., Food, M. R., and Gabathuler, R., et al. (1996) Reactive microglia specifically associated with Alzheimer’s disease brain tissue express melanotransferrin.Brain Res.712 (1), 122–126.

    Article  PubMed  CAS  Google Scholar 

  44. Connor, J.R.,Menzies, S. L., St Martin, M. S., and Mufson, E. J. (1991) A histochemical study of iron, transferrin, and ferritin in Alzheimer’s diseased brains.J. Neurosci. Res. 31(1), 75–83.

    Google Scholar 

  45. Wood, J. G. and Zinsmeister, P. (1991) Tyrosine phosphorylation systems in Alzheimer’s disease pathology.Neurosci. Lett 121 (1–2), 12–16.

    Article  PubMed  CAS  Google Scholar 

  46. Yamada, T., Miyazaki, K., Koshikawa, N., Takahashi, M., Akatsu, H., and Yamamoto T. (1995) Selective localization of gelatinase A, an enzyme degrading beta-amyloid protein, in white matter microglia and in Schwann cells.Acta Neuropathol.89 (3), 199–203.

    Google Scholar 

  47. Yamada, T., Kawamata, T., Walker, D. G., and McGeer, P. L.(1992)Vimentin immunoreactivity in normal and pathological human brain tissue.Acta Neuropathol.84(2), 157–162.

    Google Scholar 

  48. Christie, R. H., Freeman, M., and Hyman, B. T.(1996)Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer’s disease.Am. J. Pathol. 148(2), 399–403.

    Google Scholar 

  49. Christie, R. H., Chung, H., Rebeck, G. W., Strickland, D., and Hyman, B. T. (1996) Expression of the verly-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer’s disease.J. Neuropathol. Exp Neurol.55 (4), 491–498.

    Google Scholar 

  50. Akiyama, H., Ikeda, K., Kondo, H., Kato, M., and McGeer, P. L. (1993) Microglia express the type2 plasminogen activator inhibitor in the brain of control subjects and patients with Alzheimer’s disease.Neurosci. Lett.164(1-2), 233–235.

    Google Scholar 

  51. Akiyama, H., Kondo, H., Ikeda, K., Arai, T., Kato, M., and McGeer, P. L. (1995) Immunohistochemical detection of coagulation factor XIIIa in postmortem human brain tissue.Neurosci. Lett. 202, 29–32.

    Article  PubMed  CAS  Google Scholar 

  52. Gehrmann, J., Banati, R. B., and Kreutzberg, G. W. (1993) Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules.J. Neuroimmunol 48 (2), 189–198.

    Article  PubMed  CAS  Google Scholar 

  53. Charron, D. J. and McDevitt, H. O. (1979) Analysis of HLA-D region-associated molecules with monoclonal antibodies.Proc. Natl. Acad. Sci. USA 76, 6567–6571.

    Article  PubMed  CAS  Google Scholar 

  54. Colloby, P. S., West, K. P., and Fletcher, A. (1992)Is poor prognosis really related to HLA-DR expression by melanoma cells.Histopathology 20 (5), 411–416.

    CAS  Google Scholar 

  55. Mattiace, L. A., Davies, P., and Dickson, D. W. (1990) Detection of HLA-DR on microglia in the human brain is a function of both clinical and technical factors.Am. J. Pathol 136 (5), 1101–1114.

    PubMed  CAS  Google Scholar 

  56. Carpenter, A. F., Carpenter, P. W., and Markesbery, W. R. (1993) Morphometric analysis of microglia in Alzheimer’s disease.J. Neuropathol Exp. Neurol 52 (6), 601–608.

    Article  PubMed  CAS  Google Scholar 

  57. McGeer, P. L., Itagaki, S., Boyes, B. E., and McGeer, E. G.(1988) Reactive micro-glia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains.Neurology 38, 1285–1291.

    Google Scholar 

  58. Ulvestad, E., Williams, K., Bo, L., Trapp, B., Antel, J., and Mork, J. (1994) HLA class II molecules (HLA-DR, -DP, -DQ) on cells in the human CNS studied in situ and in vitro.Immunology 82 (4), 535–541.

    PubMed  CAS  Google Scholar 

  59. Kawamata, T., Akiyama, H., Yamada, T., and McGeer, P. L. (1992) Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue.Am. J. Pathol 140 (3), 691–707.

    PubMed  CAS  Google Scholar 

  60. Schwab, C., Steele, J. C., and McGeer, P. L. (1996) Neurofibrillary tangles of guam parkinson-dementia are associated with reactive microglia and complement proteins.Brain Res.707 (2), 196–205.

    Article  PubMed  CAS  Google Scholar 

  61. Muhleisen, H., Gehrmann, J., and Meyermann, R. (1995) Reactive microglia in Creutzfeldt-Jakob disease.Neuropathol. Appl. Neurobiol 21 (6), 505–517.

    Article  PubMed  CAS  Google Scholar 

  62. Jorgensen, M. B., Finsen, B. R., Jensen, M. B., Castellano, B., Diemer, N. H., and Zimmer, J. (1993) Microglial and astroglial reactions to ischemic and kainic acid-induced lesions of the adult rat hippocampus.Exp. Neurol 120 (1), 70–88.

    Article  PubMed  CAS  Google Scholar 

  63. Akiyama, H., Itagaki, S., and McGeer, P. L. (1988) Major histocompatibility complex antigen expression on rat microglia following epidural kainic acid lesions.J. Neurosci. Res.2 0(2), 147–157.

    Google Scholar 

  64. Rollini, P., Mach, B., and Gorski, J. (1985) Linkage map of three HLA-DR beta-chain genes: evidence for a recent duplication event.Proc. Natl. Acad. Sci. USA 82 (21), 7197–7201.

    Article  PubMed  CAS  Google Scholar 

  65. Styren, S. D., Civin, W. H., and Rogers, J. (1990) Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer’s disease brain.Exp. Neurol 110 (1), 93–104.

    Article  PubMed  CAS  Google Scholar 

  66. Imamura, K., Suzumura, A., Sawada, M., Mabuchi, C., and Marunouchi, T. (1994) Induction of MHC class II antigen expression on murine microglia by interleukin-3.J. Neuroimmunol 55 (2), 119–125.

    Article  PubMed  CAS  Google Scholar 

  67. Loughlin, A. J., Woodroofe, M. N., and Cuzner, M. L. (1992) Regulation of Fc receptor and major histocompatibility complex antigen expression on isolated rat microglia by tumour necrosis factor, interleukin-1 and lipopolysaccharide: effects on interferon-gamma induced activation.Immunology 75, 170–175.

    PubMed  CAS  Google Scholar 

  68. Hayashi, M., Dorf, M. E., and Abromson-Leeman, S. (1993) Granulocyte-macrophage colony stimulating factor inhibits class II major histocompatibility complex expression and antigen presentation by microglia.J. Neuroimmunol 48 (1), 23–32.

    Article  PubMed  CAS  Google Scholar 

  69. Mildenberger, M., Beach, T. G., McGeer, E. G., and Ludgate, C. M. (1990) An animal model of prophylactic cranial irradiation: histologic effects acute, early and delayed stages.Int. J. Radiat. Oncol. Biol. Physic 18 (5), 1051–1060.

    Article  CAS  Google Scholar 

  70. Gebicke-Haerter, P. J., Appel, K., Taylor, G. D., Schobert, A., Rich, I. N., Northoff, H., and Berger, M. (1994) Rat microglial interleukin-3.J. Neuroimmunol 50 (2), 203–214.

    Article  PubMed  CAS  Google Scholar 

  71. Eneroth, A., Kristensson, K., Ljungdahl, A., and Olsson T. (1991) Interferongamma-like immunoreactivity in developing rat spinal ganglia neurons in vivo and in vitro.J. Neurocytol 20 (3), 225–231.

    Article  PubMed  CAS  Google Scholar 

  72. Olsson, T., Kelic, S., Edlund, C., Bakhiet, M., Hojeberg, B., van der Meide, P. H., Ljungdahl, A., and Kristensson, K. (1994) Neuronal interferon-gamma immunoreactive molecule: bioactivities and purification.Eur. J. Immunol 24 (2), 308–314.

    Article  PubMed  CAS  Google Scholar 

  73. Cannella, B. and Raine, C. S. (1995) The adhesion molecule and cytokine profile of multiple sclerosis lesions.Ann. Neurol 37, 424–435.

    Article  PubMed  CAS  Google Scholar 

  74. Itagaki, S., McGeer, P. L., and Akiyama, H. (1988) Presence of T-cytotoxic suppressor and leucocyte common antigen cells in Alzheimer’s disease brain tissue.Neurosci. Lett 91 (3), 59–64.

    Article  Google Scholar 

  75. Schluesener, H. J., Seid, K., Kretzschmar, J., and Meyermann, R. (1996) Leukocyte chemotactic factor, a natural ligand to CD4, is expressed by lymphocytes and micro-glial cells of the MS plaque.J. Neurosci. Res. 44, 606–611.

    Article  PubMed  CAS  Google Scholar 

  76. DeSimone, R., Giampaolo, A., Giometto, B., Gallo, P., Levi, G., Peschle, C., and Aloisi, F. (1995) The costimulatory molecule B7 is expressed on human microglia in culture and in multiple sclerosis acute lesions.J. Neuropathol. Exp. Neurol 54 (2), 175–187.

    Article  CAS  Google Scholar 

  77. Itagaki, S., McGeer, P. L., Akiyama, H., Zhu, S., and Selkoe, D. (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease.J. Neuroimmunol 24 (3), 173–182.

    Article  PubMed  CAS  Google Scholar 

  78. Maat, S. M., Rozemuller, A. J., van, D. S., Haan, J., Eikelenboom, P., and Roos, R. A. (1994) Microglia in diffuse plaques in hereditary cerebral hemorrhage with amyloidosis (Dutch). An immunohistochemical study.J. Neuropathol. Exp. Neurol 53 (5), 483–491.

    Article  Google Scholar 

  79. Araujo, D. M. and Cotman, C. W. (1992) Beta-amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer’s disease.Brain Res.569 (1), 141–145.

    Article  PubMed  CAS  Google Scholar 

  80. Haga, S., Ikeda, K., Sato, M., and Ishii, T. (1993) Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells.Brain Res.601 (1–2), 88–94.

    Article  PubMed  CAS  Google Scholar 

  81. Klegeris, A., Walker, D. G., and McGeer, P. L. (1994) Activation of macrophages by Alzheimer ß amyloid peptide.Biochem. Biophys. Res. Commun 199 (2), 984–991.

    Article  PubMed  CAS  Google Scholar 

  82. Meda, L., Cassatella, M. A., and Szendrei, G. I., et al. (1995) Activation of micro-glial cells by beta-amyloid protein and interferon-gamma.Nature 374 (6523), 647–650.

    Article  PubMed  CAS  Google Scholar 

  83. Hynes, R. O. (1992) Integrins: versatility, modulation, and signaling in cell adhesion [Review].Cell 69, 11–25.

    Article  PubMed  CAS  Google Scholar 

  84. Ishii, T. and Haga, S. (1984) Immuno-electron-microscopic localization of complements in amyloid fibrils of senile plaques.Acta Neuropathol.63 (4), 296–300.

    Article  PubMed  CAS  Google Scholar 

  85. McGeer, P, L„ Akiyama, H„ Itagaki, S., and McGeer, E. G. (1989) Activation of the classical complement pathway in brain tissue of Alzheimer patients.Neurosci. Lett 107 (1–3), 341–346.

    CAS  Google Scholar 

  86. Eikelenboom, P., Hack, C. E., Rozemuller, J. M., and Stam, F. C. (1989) Complement activation in amyloid plaques in Alzheimer’s dementia.Virchows Arch. B,Cell Pathol. Including Mol. Pathol 56 (5), 259–262.

    CAS  Google Scholar 

  87. Nathan, C., Srimall, S., and Farber, C., et al. (1989) Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/ CD18 integrins.J. Cell Biol 109, 1341–1349.

    Article  PubMed  CAS  Google Scholar 

  88. Davis, G. (1992) The Mac-1 and p150,95 02 integrins bind denatured proteins to mediate leukocyte cell-substrate adhesion.Exp. Cell Res 200, 242–252.

    Article  PubMed  CAS  Google Scholar 

  89. Rogers, J., Cooper, N. R., and Webster, S., et al. (1992) Complement activation by beta-amyloid in Alzheimer disease.Proc. Natl. Acad. Sci. USA 89(21), 10,016–10, 020.

    Google Scholar 

  90. Prineas, J. W. and Graham, J. S. (1981) Multiple sclerosis: Capping of surface immunoglobulin G on macrophages engaged in myelin breakdown.Ann. Neurol 10, 149–158.

    Article  PubMed  CAS  Google Scholar 

  91. Okumura, M. and Thomas, M. L. (1995) Regulation of immune function by protein tyrosine phosphatases [Review].Curr. Opinion Immunol 7 (3), 312–319.

    Article  CAS  Google Scholar 

  92. Chao, C. C., Hu, S., Frey, W. H., II, Ala, T. A., Tourtellotte, W. W., and Peterson, P. K. (1994) Transforming growth factor beta in Alzheimer’s disease.Clin. Diagn. Lab. Immunol 1 (1), 109–110.

    PubMed  CAS  Google Scholar 

  93. Flanders, K. C., Lippa, C. F., Smith, T. W., Pollen, D. A., and Sporn, M. B. (1995) Altered expression of transforming growth factor-ß in Alzheimer’s disease.Neurology 45, 1561–1569.

    Article  PubMed  CAS  Google Scholar 

  94. Lippa, C.F., Smith, T. W., and Flanders, K. C. (1995) Transforming growth factorbeta—neuronal and glial expression in CNS degenerative diseases.Neurodegeneration 4 (4), 425–432.

    Article  PubMed  CAS  Google Scholar 

  95. Lee, S. C., Liu, W., Brosnan, C. F., and Dickson, D. W. (1994) GM-CSF promotes proliferation of human fetal and adult microglia in primary cultures.Glia 12 (4), 309–318.

    Article  PubMed  CAS  Google Scholar 

  96. Lassmann, H., Bancher, C., Breitschopf, H., Wegiel, J., Bobinski, M., Jellinger, K., and Wisniewski, H. M. (1995) Cell death in Alzheimer’s disease evaluated by DNA fragmentation in situ.Acta Neuropathol.89 (1), 35–41.

    Article  PubMed  CAS  Google Scholar 

  97. Saito, S., Morii, T., Umekage, H., Makita, K., and Nishikawa, K., et al. (1996) Expression of the interleukin-2 receptor gamma chain on cord blood mononuclear cells.Blood 87 (8), 3344–3350.

    PubMed  CAS  Google Scholar 

  98. Giri, J. G., Kumaki, S., Ahdieh, M., Friend, D. J., and Loomis, A. et al. (1995) Identification and cloning of a novel IL-15 binding protein that is structurally related to the alpha chain of the IL-2 receptor.EMBO J.14 (15), 3654–3663.

    PubMed  CAS  Google Scholar 

  99. Lee, Y-B., Satoh, J-I., Walker, D. G., and Kim, S. U. (1996) Interleukin-15 gene expression in human astrocytes and microglia in culture.Neuroreport 7, 1062–1066.

    Article  PubMed  CAS  Google Scholar 

  100. Chao, C.C., Hu, S., Molitor, T. W., Shaskan, E. G., Peterson, P. K. (1992) Activated microglia mediate neuronal cell injury via a nitric oxide mechanism.J. Immunol 149 (8), 2736–2741.

    PubMed  CAS  Google Scholar 

  101. Boje, K. M. and Arora, P. K. (1992) Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death.Brain Res 587 (2), 250–256.

    Article  PubMed  CAS  Google Scholar 

  102. Hu, S., Chao, C. C., Khanna, K. V., Gekker, G., Peterson, P. K., and Molitor, T. W. (1996) Cytokine and free radical production by porcine microglia.Clin. Immunol. Immunopathol 78 (1), 93–96.

    Article  PubMed  CAS  Google Scholar 

  103. Colasanti, M., Dipucchio, T., and Persichini, T., et al. (1995) Inhibition of inducible nitric oxide synthase mRNA expression by basic fibroblast growth factor in human microglial cells.Neurosci. Lett 195 (1), 45–48.

    Article  PubMed  CAS  Google Scholar 

  104. Lee, S. C., Dickson, D. W., Liu, W., Brosnan, C. F. (1993) Induction of nitric oxide synthase activity in human astrocytes by interleukin-1 beta and interferon-gamma. J. Neuroimmunol.46(1–2), 19–24.

    Google Scholar 

  105. Bo, L., Dawson, T. M., Wesselingh, S., Mork, S., and Choi, S., et al. (1994) Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains.Ann. Neurol 36, 778–786.

    Article  PubMed  CAS  Google Scholar 

  106. Remold-O’Donnell, E. and Parent, D. (1994) Two proteolytic pathways for down-regulation of the barrier molecule CD43 of human neutrophils.J. Immunol 152 (7), 3595–3605.

    PubMed  Google Scholar 

  107. Remold-O’Donnell, E. and Parent, D. (1995) Downregulation of neutrophil CD43 by opsonized zymosan.Blood 85 (2), 337–342.

    PubMed  Google Scholar 

  108. Remold-O’Donnell, E. and Parent, D. (1995) Specific sensitivity of CD43 to neutro-phil elastase.Blood 86 (6), 2395–2402.

    PubMed  Google Scholar 

  109. Tiisala, S., Majuri, M. L., Carpen, O., and Renkonen, R. (1994) Enhanced ICAM1-dependent adhesion of myelomonocytic cells expressing increased levels of beta 2-integrins and CD43.Scand. J. Immunol 39 (3), 249–256.

    Article  PubMed  CAS  Google Scholar 

  110. Green, S. P. and Philips, W. A. (1994) Activation of the macrophage respiratory burst by phorbol myristate acetate: evidence for both tyrosine-kinase-dependent and independent pathways.Biochem. Biophys. Acta 1222, 241–248.

    Article  PubMed  CAS  Google Scholar 

  111. Pei, J-J., Sersen, E., Iqbal, K., and Grundke-Iqbal, I. (1994) Expression of protein phosphatases (PP-1, PP-2A, PP-2B and PTP-1B) and protein kinases (MAP kinase and P34cdc2) in the hippocampus of patients with Alzheimer disease and normal aged individuals.Brain Res.655, 70–76.

    Article  PubMed  CAS  Google Scholar 

  112. Smith, M. A., Kalaria, R. N., and Perry, G. (1993) a-Trypsin immunoreactivity in Alzheimer disease.Biophys. Biochem. Res. Commun 193, 579–584.

    Google Scholar 

  113. Nakamura, Y., Takeda, M., Suzuki, H., and Hattori, H., et al. (1991) Abnormal distribution of cathepsins in the brain of patients Alzheimer’s disease.Neurosci. Lett 30 (2), 195–198.

    Article  Google Scholar 

  114. Abraham, C. R., Selkoe, D. J., and Potter, H. (1988) Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer’s disease.Cell 52 (4), 487–501.

    Article  PubMed  CAS  Google Scholar 

  115. Gollin, P. A., Kalaria, R. N., Eikelenboom, P., Rozemuller, A., and Perry, G. (1992) Alpha 1-antitrypsin and alpha 1-antichymotrypsin are in the lesions of Alzheimer’s disease.Neuroreport 3 (2), 201–203.

    Article  PubMed  CAS  Google Scholar 

  116. Van Gool, D., De Strooper, B., Van Leuven, F., Triau E., and Dom, R. (1993) Alpha 2-Macroglobulin expression in neuritic-type plaques in patients with Alzheimer’s disease.Neurobiol. Aging 14 (3), 233–237.

    Article  PubMed  Google Scholar 

  117. Peress, N., Perillo, E., and Zucker, S. (1995) Localization of tissue inhibitor of matrix metalloproteinases in Alzheimer’s disease and normal brain.J. Neuropathol Exp. Neurol 54, 16–22.

    Article  PubMed  CAS  Google Scholar 

  118. Bernstein, H. G., Rinne, R., Kirschke, H., Jarvinen, M., Knofel, B., and Rinne, A. (1994) Cystatin A-like immunoreactivity is widely distributed in human brain accu-mulates in neuritic plaques of Alzheimer disease subjects.Brain Res. Bull 33 (5), 477–481.

    Article  PubMed  CAS  Google Scholar 

  119. Tago, H., McGeer, P. L., and McGeer, E. G. (1987) Acetylcholinesterase fibers and the development of senile plaques.Brain Res.406 (1–2), 363–369.

    Article  PubMed  CAS  Google Scholar 

  120. Moran, M. A., Mufson, E. J., and Gomez, R. P. (1993) Colocalization of cholinesterases with beta amyloid protein in aged and Alzheimer’s brains.Acta Neuropathol.85 (4), 362–369.

    Article  PubMed  CAS  Google Scholar 

  121. Rebeck, G. W., Harr, S. D., Strickland, D. K., and Hyman, B. T. (1995) Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein.Ann. Neurol 37 (2), 211–217.

    CAS  Google Scholar 

  122. Akiyama, H., Ikeda, K., Kondo, H., and McGeer, P. L. (1992) Thrombin accumulation in brains of patients with Alzheimer’s disease.Neurosci. Lett 146 (2), 152–154.

    Article  PubMed  CAS  Google Scholar 

  123. Yasuhara, O., Walker, D. G., and McGeer, P. L. (1994) Hageman factor and its binding sites are present in senile plaques of Alzheimer’s disease.Brain Res.654 (2), 234–240.

    Article  PubMed  CAS  Google Scholar 

  124. Shinohara, H., Inaguma, Y., Goto, S., Inagaki, T., and Kato, K. (1993) Alpha B crystallin and HSP28 are enhanced in the cerebral cortex of patients with Alzheimer’s disease.J. Neurol. Sci 119 (2), 203–208.

    Article  PubMed  CAS  Google Scholar 

  125. Akiyama, H., Yamada, T., Kawamata, T., and McGeer, P. L. (1991) Association of amyloid P component with complement proteins in neurologically diseased brain tissue.Brain Res.548 (1–2), 349–352.

    Article  PubMed  CAS  Google Scholar 

  126. Kalaria, R. N. and Perry, G. (1993) Amyloid P component and other acute-phase proteins associated with cerebellar A beta-deposits in Alzheimer’s disease.Brain Res.631 (1), 151–155.

    Article  PubMed  CAS  Google Scholar 

  127. Snow, A. D., Mar, H., and Nochlin, D., et al. (1990) Early accumulation of heparan sulfate in neurons and in the beta-amyloid protein-containing lesions of Alzheimer’s disease and Down’s syndrome.Am. J. Pathol 137 (5), 1253–1270.

    PubMed  CAS  Google Scholar 

  128. DeWitt, D. A., Silver, J., Canning, D. R., and Perry, G. (1993) Chondroitin sulfate proteoglycans are associated with the lesions of Alzheimer’s disease.Exp. Neurol 121 (2), 149–152.

    Article  PubMed  CAS  Google Scholar 

  129. Snow, A. D., Mar, H., Nochlin, D., Kresse, H., and Wight, T. N. (1992) Peripheral distribution of dermatan sulfate proteoglycans (decorin) in amyloid-containing plaques and their presence in neurofibrillary tangles of Alzheimer’s disease.J. Histochem. Cytochem 40 (1), 105–113.

    Article  PubMed  CAS  Google Scholar 

  130. Birecree, E., King, L. E., Jr., and Nanney, L. B. (1991) Epidermal growth factor and its receptor in the developing human system.Del). Brain Res 60 (2), 145–154.

    Article  CAS  Google Scholar 

  131. Tooyama, I., Kawamata, T., Akiyama, H., Moestrup, S. K., Gliemann, J., and McGeer, P. L. (1993) Immunochemical study of alpha 2 macroglobulin receptor in Alzheimer and control postmortem human brain.Mol. Chem. Neuropathol 18 (1–2), 153–160.

    Article  PubMed  CAS  Google Scholar 

  132. Cummings, B. J., Su, J. H., and Cotman, C. W. (1993) Neuritic involvement within bFGF immunopositive plaques of Alzheimer’s disease.Exp. Neurol 124 (2), 315–325.

    Article  PubMed  CAS  Google Scholar 

  133. Yasuhara, O., Muramatsu, H., and Kim, S. U., et al. (1993) Midkine, a novel neurotrophic factor, is present in senile plaques of Alzheimer disease.Biochem. Biophys. Res. Commun 192 (1), 246–251.

    Article  PubMed  CAS  Google Scholar 

  134. Huell, M., Strauss, S., Volk, B., Berger, M., and Bauer, J. (1995) Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of alzheimers disease patients.Acta Neuropathol.89 (6), 544–551.

    Article  PubMed  CAS  Google Scholar 

  135. Walker, D. G., Yasuhara, O., Patston, P. A., McGeer, E. G., and McGeer, P. L. (1995) Complement Cl inhibitor is produced by brain tissue and is cleaved in Alzheimer disease.Brain Res.675 (1–2), 75–82.

    Article  PubMed  CAS  Google Scholar 

  136. Kalaria, R. N. and Kroon, S. N. (1992) Complement inhibitor C4-binding protein in amyloid deposits containing serum amyloid P in Alzheimer’s disease.Biochem. Biophys. Res. Commun 186 (1), 461–566.

    Article  PubMed  CAS  Google Scholar 

  137. McGeer, P. L., Kawamata, T., and Walker, D. G. (1992) Distribution of clusterin in Alzheimer brain tissue.Brain Res.579 (2), 337–341.

    Article  PubMed  CAS  Google Scholar 

  138. Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., and Ikeda, K. (1991) Apo-lipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jakob disease.Brain Res.541 (1), 163–166.

    CAS  Google Scholar 

  139. van Duinen, S. G., Maat-Schieman, M. L., Bruijn, J. A., Haan, J., and Roos, R. A. (1995) Cortical tissue of patients with hereditary cerebral hemorrhage with amyloidosis (Dutch) contains various extracellular matrix deposits.Lab. Invest 73 (2), 183–189.

    PubMed  Google Scholar 

  140. Murtomaki, S., Risteli, J., Risteli, L., Koivisto, U. M., Johansson, S., and Liesi, P. (1992) Laminin and its neurite outgrowth-promoting domain in the brain in Alzheimer’s disease and Down’s syndrome patients.J. Neurosci. Res 32 (2), 261–273.

    Article  PubMed  CAS  Google Scholar 

  141. Zhan, S. S., Veerhuis, R., Kamphorst, W., and Eikelenboom, P. (1995) Distribution of beta amyloid associated proteins in plaques in Alzheimer’s disease and in the non-demented elderly.Neurodegeneration 4 (3), 291–297.

    Article  PubMed  CAS  Google Scholar 

  142. Kawamata, T., Tooyama, I., Yamada, T., Walker, D. G., and McGeer, P. L. (1993) Lactotransferrin immunocytochemistry in Alzheimer and normal human brain.Am. J. Pathol 142 (5), 1574–1585.

    PubMed  CAS  Google Scholar 

  143. Kalaria, R. N., Golde, T. E., Cohen, M. L., and Younkin, S. G. (1991) Serum amyloid P in Alzheimer’s disease. Implications for dysfunction of the blood-brain barrier.Ann. NY Acad. Sci 640, 145–148.

    PubMed  CAS  Google Scholar 

  144. Gupta, B. R., Frederickson, R. C., and Brunden, K. R. (1995) Proteoglycanmediated inhibition of A beta proteolysis. A potential cause of senile plaque accumulation.J. Biol. Chem.270(31), 18,666–18, 671.

    Google Scholar 

  145. Ard, M. D., Cole, G. M., Wei, J., Mehrle, A. P., and Fratkin, J. D. (1996) Scavenging of Alzheimers amyloid beta-protein by microglia in culture.J. Neurosci. Res 43 (2), 190–202.

    Article  PubMed  CAS  Google Scholar 

  146. Mackenzie, I. R., Hao, C., and Munoz, D. G. (1995) Role of microglia in senile plaque formation.Neurobiol. Aging 16 (5), 797–804.

    Article  PubMed  CAS  Google Scholar 

  147. Fukumoto, H., Asamiodaka, A., Suzuki, N., and Iwatsubo, T. (1996) Association of A-beta-1–40 positive senile plaques with microglial cells in the brains of patients with Alzheimers disease and in non-demented aged individuals.Neurodegeneration 5 (1), 13–17.

    Article  PubMed  CAS  Google Scholar 

  148. Wisniewski, H. M. and Weigel, J. (1993) Migration of perivascular cells into the neuropil and their involvement in 13-amyloid plaque formation.Acta Neuropathol.85, 586–595.

    Article  PubMed  CAS  Google Scholar 

  149. Frackowiak, J., Wisniewski, H. M., Wegiel, J., Merz, G. S., Iqbal, K., and Wang, K. C. (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils.Acta Neuropathol.84 (3), 225–233.

    Article  PubMed  CAS  Google Scholar 

  150. The IFNB multiple sclerosis study group. (1993) Interferon-3-lb is effective in relapsing remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double blind, placebo-controlled trial.Neurology 43, 655–661.

    Article  Google Scholar 

  151. Giulian, D., Haverkamp, L. J., Li, J., Karshin, W. L., Yu, J., Tom, D., Li, X., and Kirkpatrick, J. B. (1995) Senile plaques stimulate microglia to release a neurotoxin found in alzheimer brain.Neurochem. Int. 27 (1), 119–137.

    Article  PubMed  CAS  Google Scholar 

  152. Giulian, D., Haverkamp, L. J., Yu, J. H., Karshin, W., Tom, D., Li, J., Kirkpatrick, J., Kuo, L. M., and Roher, A. E. (1996) Specific domains of beta-amyloid from Alzheimer plaque elicit neuron killing in human microglia.J. Neurosci. 16 (19), 6021–6037.

    PubMed  CAS  Google Scholar 

  153. McGeer, P. L., McGeer, E., Rogers, J., and Sibley, J. (1990) Anti-inflammatory drugs and Alzheimer disease [Letter].Lancet 335 (8696), 1037.

    Article  PubMed  CAS  Google Scholar 

  154. Andersen, K., Launer, L. J., and Ott, A., et al. (1995) Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer’s disease? The Rotterdam Study.Neurology 45, 1441–1445.

    Article  PubMed  CAS  Google Scholar 

  155. Anonymous. (1994) The Canadian Study of Health and Aging: risk factors for Alzheimer’s disease in Canada.Neurology 44 (11), 2073–2080.

    Article  Google Scholar 

  156. Myllykangas-Luosujarvi, R. and Isomaki, H. (1994) Alzheimer’s disease and rheumatoid arthritis.Br. J. Rheumatol 33 (5), 501–502.

    Article  PubMed  CAS  Google Scholar 

  157. Breitner, J. C., Gau, B. A., Welsh, K. A., Plassman, B. L., McDonald, W. M., Helms, M. J., and Anthony, J. C. (1994) Inverse association of anti-inflammatory treatments and Alzheimer’s disease: initial results of a co-twin control study.Neurology 44 (2), 227–232.

    Article  PubMed  CAS  Google Scholar 

  158. Rogers, J., Kirby, L. C., Hempelman, S. R., et al. (1993) Clinical trial of indomethacin in Alzheimer’s disease.Neurology 43 (8), 1609–1611.

    Article  PubMed  CAS  Google Scholar 

  159. Parkinson, F. E., Rudolphi, K. A., and Fredholm, B. B. (1994) Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischemia [Review].Gen. Pharmacol 25 (6), 1053–1058.

    Article  PubMed  CAS  Google Scholar 

  160. Nabeshima, T., Nitta, A., Fuji, K., Kameyama, T., and Hasegawa, T. (1994) Oral administration of NGF synthesis stimulators recovers reduced brain NGF content in aged rats and cognitive dysfunction in basal-forebrain-lesioned rats.Gerontology 40 (52), 46–56.

    Article  PubMed  CAS  Google Scholar 

  161. Banati, R. B., Schubert, P., Rothe, G., Gehrmann, J., Rudolphi, K., Valet, G., and Kreutzberg, G. W. (1994) Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline.J. Cereb. Blood Flow Metab 14 (1), 145–149.

    Article  PubMed  CAS  Google Scholar 

  162. Moller, H. J., Maurer, I., and Saletu, B. (1994) Placebo-controlled trial of the xanthine derivative propentofylline in dementia.Pharmacopsychiatry 27 (4), 159–1665

    Article  PubMed  CAS  Google Scholar 

  163. Breitner, J. C. S. (1996) The role of anti-inflammatory drugs in the prevention and treatment of Alzheimers disease [Review].Ann. Rev. Med 47, 401–11.

    Article  PubMed  CAS  Google Scholar 

  164. Abramson, S. B. and Weissman, G. (1989) The mechanisms of action of nonsteroidal antiinflammatory drugs.Arthritis Rheum.32 (1), 1–9

    Article  PubMed  CAS  Google Scholar 

  165. Korotzer, A. R., Watt, J., Cribbs, D., Tenner, A. J., Burdick, D., Glabe, C., and Cotman, C. W. (1995) Cultured rat microglia express Clq and receptor for Clq: implications for amyloid effects on microglia.Exp. Neurol 134 (2), 214–221.

    Article  PubMed  CAS  Google Scholar 

  166. Malhotra, R., Thiel, S., Reid, K. B., and Sim, R. B. (1990) Human leukocyte Clq receptor binds other soluble proteins with collagen domains.J. Exp. Med 172 (3), 955–959.

    Article  PubMed  CAS  Google Scholar 

  167. Diamond, M. S. and Springer, T. A. (1993) A subpopulation of Mac-1 (CD11b/ CD18) molecules mediates neutrophil adhesion to ICAM-1 and fibrinogen.J. Cell Biol 120 (2), 545–556.

    Article  PubMed  CAS  Google Scholar 

  168. Brett, J., Schmidt, A. M., Yan, S. D., Zou, Y. S., Weidman, E., Pinsky, D., Nowygrod, R., Neeper, M., Przysiecki, C., and Shaw, A., et al. (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues.Am. J. Pathol. 143 (6), 1699–1712.

    PubMed  CAS  Google Scholar 

  169. Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., Migheli, A., Nawroth, P., Stern, D., and Schmidt, A. M. (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease.Nature 382, 685–692.

    Article  PubMed  CAS  Google Scholar 

  170. Yan, S. D., Yan, S. F., Chen, X., Fu, J., Chen, M., Kuppusamy, P., Smith, M. A., and Perry, G., et al. (1995) Non-enzymatically glycated tau in alzheimers disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide.Nature Med.1 (7), 693–699.

    Article  PubMed  CAS  Google Scholar 

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Walker, D.G. (1998). Inflammatory Markers in Chronic Neurodegenerative Disorders with Emphasis on Alzheimer’s Disease. In: Wood, P.L. (eds) Neuroinflammation. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-473-3_2

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