Inflammatory Mediators in Alzheimer’s Disease

  • Joseph Rogers
  • Stephen O’Barr
Part of the Contemporary Neuroscience book series (CNEURO)


In 1984, when our laboratory first began conducting research on inflammation and Alzheimer’s disease (AD) (1), the brain was still widely considered to be immunologically privileged (reviewed in ref 2). Now, a virtual textbook of inflammatory mediators have been shown to be present in the central nervous system (CNS) or expressed by CNS cells in culture (Table 1). Most of these molecules are known to be increased in expression in AD limbic and neocortex compared to similar samples from nondemented elderly (ND) patients. By understanding the functions of inflammatory mediators in general, and their interactions with AD pathology in particular, a better appreciation of their pathogenic potential may be fostered.


Inflammatory Mediator Alzheimer Disease Senile Plaque Neural Cell Adhesion Molecule Toxic Shock Syndrome 
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.


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  1. 1.
    Rogers, J., Singer, R. H., Luber-Narod, J., and Bassell, G. J. (1986) Neurovirologic and neuroimmunologic considerations in Alzheimer’s disease, Neurosci. Abstr. 12, 944.Google Scholar
  2. 2.
    Hickey, W. F., Hsu, B. L., and Kimura, H. (1991) T-lymphocyte entry into the central nervous system, J. Neurosci. Res. 28, 254–260.PubMedGoogle Scholar
  3. 3.
    Tooyama, I., Kimura, H., Akiyama, H., and McGeer, P. L. (1990) Reactive microglia express class and class II major histocompatibility antigens in Alzheimer disease, Brain Res. 23, 273–280.Google Scholar
  4. 4.
    McGeer, P. L., Akiyama, H., Itagaki, S., and McGeer, E. G. (1989) Immune system response in Alzheimer’s disease, Can. J. Neurol. Sci. 16, 516–527.PubMedGoogle Scholar
  5. 5.
    Eikelenboom, P., Rozemuller, J. M., Kraal, G., Stam, F. C., McBride, P. A., Bruce, M. E., and Fraser, H. (1991) Cerebral amyloid plaques in Alzheimer’s disease but not in scrapieaffected mice are closely associated with a local inflammatory process, Virchows Archives B Cell Pathol. 60, 329–336.Google Scholar
  6. 6.
    Itagaki, S., McGeer, P. L., and Akiyama, H. (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer’s disease, J. Neuroimmunol. 24, 173–182.PubMedGoogle Scholar
  7. 7.
    Luber-Narod, J. and Rogers, J. (1988) Immune system associated antigens expressed by cells of the human central nervous system, Neurosci. Lett. 94, 17–22.PubMedGoogle Scholar
  8. 8.
    Mattiace, L. A., Davies, P., and Dickson, D. W. (1990) Detection of HLA-DR on microglia in postmortem human brain is a function of clinical and technical factors, Am. J Pathol. 136, 1101–1114.PubMedGoogle Scholar
  9. 9.
    McGeer, P. L., Itagaki, S., Tago, H., and McGeer, E. G. (1987) Reactive microglia in patients with senile dementia of the Alzheimer type are positive for histocompatibility glycoprotein HLA-DR, Neurosci. Lett. 79, 195–200.PubMedGoogle Scholar
  10. 10.
    Rogers, J., Luber-Narod, J., Styren S. D., and Civin, W. H. (1988) Expression of immune systemassociated antigen by cells of the human central nervous system. Relationship to the pathology of Alzheimer disease, Neurobiol. Aging 9, 339–349.PubMedGoogle Scholar
  11. 11.
    Styren, S. D., Civin, W. H., and Rogers, J. (1990) Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer disease brain, Exp. Neurol. 110, 93–104.PubMedGoogle Scholar
  12. 12.
    Abraham, C. R., Selkoe, D. J., and Potter, H. (1988) Immunochemical identification of the serine protease inhibitor, a i -antichymotrypsin in the brain amyloid deposits of Alzheimer’s disease, Cell 52, 487–501.PubMedGoogle Scholar
  13. 13.
    Abraham, C. R., Shirahama, T., and Potter, H. (1990) Antichymotrypsin is associated solely with amyloid deposits containing the 0-protein, Neurobiol. Aging 11, 123–129.PubMedGoogle Scholar
  14. 14.
    Gollin, P. A., Kalaria, R. N., Eikelenboom, P., Rozemuller, A., and Perry, G. (1992) Antitrypsin and a1-antichymotrypsin are in the lesions of Alzheimer’s disease, Neuroreport 3, 201–203.PubMedGoogle Scholar
  15. 15.
    Rozemuller, J. M., Stam, F. C., and Eikelenboom, P. (1990) Acute phase proteins are present in amorphous plaques in the cerebral but not in the cerebellar cortex of patients with Alzheimer’s disease, Neurosci. Lett. 119, 75–78.PubMedGoogle Scholar
  16. 16.
    Rozemuller, J. M., Abbink, J. J., Kamp, A. M., Stam, F. C., Hack, C. E., and Eikelenboom, P. (1991) Distribution pattern and fuctional state of alpha 1-antichymotrypsin in plaques and vascular amyloid in Alzheimer’s disease, Acta Neuropathol. 82, 200–207.PubMedGoogle Scholar
  17. 17.
    Licastro, F., Morini, M. C., Polazzi, E., and Davis, L. J. (1995) Increased serum alpha 1antichymotrypsin in patients with probable Alzheimer’s disease: an acute phase reaction without the peripheral acute phase response, J. Neuroimmunol. 57, 71–75.PubMedGoogle Scholar
  18. 18.
    Licastro, F., Parnetti, L., Morini, M. C., Davis, L. J., Cucinotta, D., Gaiti, A., and Senin, U. (1995) Acute phase reactant alpha 1-antichymotrypsin is increased in cerebrospinal fluid and serum of patients with probable Azlheimer disease, Alzheimer’s Disease and Associated Disorders 9, 112–118.Google Scholar
  19. 19.
    Lieberman, J., Schleissner, L., Tachiki, K. H., and Kling, A. S. (1995) Serum alpha 1-antichymotrypsin level as a marker for Alzheimer-type dementia, Neruobiol. Aging 16, 747–753.Google Scholar
  20. 20.
    Das, S. and Potter, H. (1995) Expression of the Alzheimer amyloid-promoting factor anitchymotrypsin is induced in human astrocytes by IL-1, Neuron 14, 447–456.PubMedGoogle Scholar
  21. 21.
    Bauer, J., Strauss, S., Schreiter-Gasser, U., Ganter, U., Schlegel, P., Witt, I., Volk, B., and Berger, M. (1991) Interleukin-6 and a2-macroglobulin indicate an acute-phase state in Alzheimer’s disease cortices, FEBSLett. 285, 111–114.Google Scholar
  22. 22.
    Van Gool, D., De Strooper, B., Van Leuven, F., Triau, E., and Dom, R. (1993) a2-macroglobulin expression in neuritic-type plaques in patients with Alzheimer’s disease, Neurobiol. Aging 14, 233–237.Google Scholar
  23. 23.
    Wood, J. A., Wood, P. L., Ryan, R., Graff-Radford, N. R., Pilapil, C., Robitaille, Y., and Quirion, R.(1993) Cytokine indices in Alzheimer’s temporal cortex: no changes in mature IL-1 b or IL-1 RA but increases in the associated acute phase proteins IL-6, a2-macroglobulin and C-reactive protein, Brain Res. 629, 245–252.PubMedGoogle Scholar
  24. 24.
    Gebicke-Haerter, P. J., Bauer, J., Brenner, A., Gerok, W. (1987) Alpha 2-macroglobulin synthesis in an astrocyte subpopulation, J. Neurochem. 49, 1139–1145.PubMedGoogle Scholar
  25. 25.
    Coria, F., Castano, E., Prelli, F., Larrondo-Lillo, M., van Duinen, S., Shelanski, M. L., and Frangione, B. (1988) Isolation and characterization of amyloid P component from Alzheimer’s disease and other types of cerebral amyloidosis, Lab. Invest. 58, 454–458.PubMedGoogle Scholar
  26. 26.
    Duong, T., Pommier, E. C., and Schiebel, A. B. (1989) Immunodetection of the amyloid P component in Alzheimer’s disease, Acta Neuropathol. 78, 429–437.PubMedGoogle Scholar
  27. 27.
    Kalaria, R. N. and ‘Croon, S. N. (1992) Complement inhibitor C4-binding protein in amyloid deposits containing serum amyloid P in Alzheimer’s disease, Biochem. Biophys. Res. Commun. 186, 461–466.PubMedGoogle Scholar
  28. 28.
    Akiyama, H., Yamada, T., Dawamata, T., and McGeer, P. L. (1991) Association of amyloid P component with complement proteins in neurologically diseased tissue, Brain Res. 548, 349–352.PubMedGoogle Scholar
  29. 29.
    Smith, M. A., Kalaria, R. N., and Perry, G. (1993) Alpha 1-trypsin immunoreactivity in Alzheimer disease, Biochem. Biophys. Res. Commun. 193, 579–584.PubMedGoogle Scholar
  30. 30.
    Iwamoto, N., Nishiyama, E., Ohwada, J., and Arai, H. (1994) Demonstration of CRP immunoreactivity in brains of Alzheimer’s disease: immunohistochemical study using formic acid pretreatment of tissue sections, Neurosci. Lett. 177, 23–26.PubMedGoogle Scholar
  31. 31.
    Strauss, S., Bauer, J., Ganter, U., Jonas, U., Berger, M., and Volk, B. (1992) Detection of interleukin-6 and a2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer’s disease patients, Lab. Invest. 66, 223–230.PubMedGoogle Scholar
  32. 32.
    Sheng, J. G., Mrak, R. E., and Griffin, W. S. (1995) Microglial interleukin-1 alpha expression in brain regions in Alzheimer’s disease: correlation with neuritic plaque distribution, Neuropathol. Appl. Neurobiol. 21, 290–301.PubMedGoogle Scholar
  33. 33.
    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, 276–281.PubMedGoogle Scholar
  34. 34.
    Walker, D. G., Kim, S. U., and McGeer, P. L. (1995) Complement and cytokine gene expression in cultured microglia derived from post-mortem human brains, J. Neurosci. Res. 40, 478–493.PubMedGoogle Scholar
  35. 35.
    Lieberman, A. P., Pitha, P. M., Shin, H. S., and Shin, M. L. (1989) Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus, Proc. Natl. Acad. Sci. USA 86, 6348–6352.PubMedGoogle Scholar
  36. 36.
    Cacabelos, R., Alvarez, X. A., Fernandez-Novoa, L., Franco A., Mangues, R., Pellicer, A., and Nishimura, T. (1994) Brain interleukin-1 beta in Alzheimer’s disease and vascular dementia, Methods Findings Exp. Clin. Pharmacol. 16, 141–145.Google Scholar
  37. 37.
    Sharif, S. F., Hariri, R. J., Chang, V. A., Barie, P. S., Wang, R. S., and Ghajar, J. B. (1993) Human astrocyte production of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6 following exposure to lipopolysaccharide endotoxin, Neurol. Res. 15, 109–112.PubMedGoogle Scholar
  38. 38.
    Gebicke-Haerter, R. J., Appel, K., Taylor, G. D., Schobert, A., Rich, I. N., Northoff, H., and Berger, M. (1994) Rat microglial interleukin-3, J. Neuroimmunol. 50, 203–214.PubMedGoogle Scholar
  39. 39.
    Swada, N., Suzumura, A., Itoh, Y., and Marunouchi, T. (1993) Production of interleukin-5 by mouse astrocytes and microglia in culture, Neurosci. Lett. 155, 175–178.Google Scholar
  40. 40.
    Shalit, F., Sredni, B., Stern, L., Kott, E., and Huberman, M. (1994) Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer’s patients, Neurosci. Lett. 174, 130–132.PubMedGoogle Scholar
  41. 41.
    Aloisi, F., Care, A., Borsellino, G., Gallo, P., Rosa, S., Bassani, A., Cabibbo, A., Testa, U., Levi, G., and Peschle, C. (1992) Production of hemolymphopoietic cytokines (IL-6, IL 8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha, J. Immunol. 149, 2358–2366.PubMedGoogle Scholar
  42. 42.
    Fillit, H., Ding, W., Buee, L., Kalman, J., Altstiel, L., Lawlor, B., and Wolf-Klein, G. (1991) Elevated circulating tumor necrosis factor levels in Alzheimer’s disease, Neurosci. Lett. 129, 318–320.PubMedGoogle Scholar
  43. 43.
    Cacabelos, R., Alverez, X. A., Franco-Maside, A., Fernandez-Novao, L., and Caamano, J. (1994) Serum tumor necrosis factor (TNF) in Alzheimer’s disease and multi-infarct dementia, Methods Findings Exp. Clin. Pharmacol. 16, 29–35.Google Scholar
  44. 44.
    Boka, G., Anglade, R, WallachL, D., Javoy-Agrid, G., Agid, Y., and Hirsch, E. C. (1994) Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson’s disease, Neurosci. Lett. 172, 151–154.Google Scholar
  45. 45.
    Mogi, M., Harada, M., Riederer, P., Narabayashi, H., Fujita, K., and Nagatsu, T. (1994) Tumor necrosis factor-a (TNF-a) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients, Neurosci. Lett. 165, 208–210.PubMedGoogle Scholar
  46. 46.
    Yamabe, T., Dhir, G., Cowan, E. P., Wolf, A. L., Bergey, G. K., Krumholz, A., Barry, E., Hoffman, R M., and Dhib-Jalbut, S. (1994) Cytokine-gene expression in measles-infected adult human glial cells, J. Neuroimmunol. 49, 171–179.PubMedGoogle Scholar
  47. 47.
    Mogi, M., Harada, M., Kondo, T., Riederer, P., Inagaki, H., Minami, M., and Nagatsu, T. (1994) Interleukin-1 ß, interleukin-6, epidermal growth factor and transforming growth factor-a are elevated in the brain from parkinsonian patients, Neurosci. Leu. 180, 147–150.Google Scholar
  48. 48.
    Chao, C. C., Hu, S., Frey, W. H., II, Ala, T. A., Tourtelotte, W. W., and Peterson, R K. (1994) Transforming growth factor beta in Alzheimer’s disease, Clin. Diagn. Lab. Immunol. 1, 109–110.PubMedGoogle Scholar
  49. 49.
    Mogi, M., Harada, M., Kondo, T., Narabayashi, H., Riederer, R, and Nagatsu, T. (1995) Transforming growth fator-beta 1 levels are elevated in the striatum and in the ventricular cerebrospinal fluid in Parkinson’s disease, Neurosci. Lett. 193, 129–132.PubMedGoogle Scholar
  50. 50.
    Hurwitz, A. A., Lyman, W. D., and Berman, J. W. (1995) Tumor necrosis factor alpha and transforming growth factor beta upregulate astrocyte expression of monocyte chemoattractant protein-1, J. Neuroimmunol. 57, 193–198.PubMedGoogle Scholar
  51. 51.
    Murphy, G. M., Jr., Jia, X. C., Song, Y., Ong, E., Shrivastava, R., Bocchini, V., Lee, Y. L., and Eng, L. F. (1995) Macrophage inflammatory protein 1-alpha mRNA expression in an immortalized microglial cell line and cortical astrocyte cultures, J. Neurosci. Res. 40, 755–763.PubMedGoogle Scholar
  52. 52.
    Brachova, L., Lue, L.-F., Schultz., J., El Rashidy, T., and Rogers, J. (1993) Association cortex, cerebellum, and serum concentrations of Clq and factor B in Alzheimer’s disease, Mol. Brain Res. 18, 329–334.Google Scholar
  53. 53.
    Eikelenboom, P., Hack, C. E., Rozemuller, J. M., and Stam, F. C. (1989) Complement activation in amyloid plaques in Alzheimer’s dementia, Virchows Archives B Cell Pathol. 56, 259–262.Google Scholar
  54. 54.
    Eikelenboom, P. and Stam, F. C. (1984) An immunohistochemical study on cerebral vascular and senile plaque amyloid in Alzheimer’s dementia, Virchows Archives B Cell Pathol. 47, 17–25.Google Scholar
  55. 55.
    Ishii, T. and Haga, S. (1984) Immuno-electron-microscopic localization of complements in amyloid fibrils of senile plaques, Acta Neuropathol. (Berl.) 63, 296–300.Google Scholar
  56. 56.
    Ishii, T., Haga, S., and Kametani, F. (1988) Presence of immunoglobulins and complements in the amyloid plaques in the brain of patients with Alzheimer’s disease, in Immunology and Alzheimer’s Disease ( Pouplard-Barthelaix, A., Emile, J., and Christen, Y., eds.), Springer-Verlag, Berlin, pp. 17–29.Google Scholar
  57. 57.
    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, 341–346.PubMedGoogle Scholar
  58. 58.
    Rogers, J., Cooper, N. R., Webster, S., Schultz, J., McGeer, P. L., Styren, S. D., Civin, W. H., Brachova, L., Bradt, B., Warcl, R, and Lieberburg, I. (1992) Complement activation by f3amyloid in Alzheimer disease, Proc. Nat. Acad. Sci. USA 89, 10016–10020.PubMedGoogle Scholar
  59. 59.
    Veerhuis, R., van der Valk, P., Janssen, I., Zhan, S. S., Van Nostrand, W. E., and Eikelenboom, P. (1995) Complement activation in amyloid plaques in Alzheimer’s disease brains does not proceed further than C3, Virchows Archives 426, 603–610.Google Scholar
  60. 60.
    Lue, L.-F. and Rogers, J. (1992) Full complement activation fails in diffuse plaques of the Alzheimer’s disease cerebellum, Dementia 3, 308–313.Google Scholar
  61. 61.
    Eikelenboom, P., Zhan, S. S., Kamphorst, W., van der Valk, P., and Rozemuller, J. M. (1994) Cellular and substrate adhesion molecules (integrins) and their ligands in cerebral amyloid plaques in Alzheimer’s disease, Virchows Archives 424, 421–427.Google Scholar
  62. 62.
    Haga, S., Ikeda, K., Sato, M., and Ishii, T. (1993) Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement 3 component by cultured microglial cells, Brain Res. 601, 88–94.PubMedGoogle Scholar
  63. 63.
    Itagaki, S., Akiyama, H., Saito, H., and McGeer, P. L. (1994) Ultrastructural localization of complement membrane attack complex (MAC)-like immunoreactivity in brains of patients with Alzheimer’s disease, Brain Res. 645, 78–84.PubMedGoogle Scholar
  64. 64.
    McGeer, P. L., Kawamata, T., and Walker, D. G. (1992) Distribution of clusterin in Alzheimer brain tissue, Brain Res. 579, 337–341.PubMedGoogle Scholar
  65. 65.
    Webster, S. D., Lue, L.-F., McKinley, M., and Rogers, J. (1992) Ultrastructural localization of complement proteins to neuronal membranes and 13-amyloid peptide containing Alzheimer’s disease pathology, Neurosci. Abstr. 18, 765.Google Scholar
  66. 66.
    Johnson, S. A., Lampert-Etchells, M., Pasinetti, G. M., Rozovsky, I., and Finch, C. E. (1992) Complement mRNA in the mammalian brain: responses to Alzheimer’s disease and experimental brain lesioning, Neurobiol. Aging 13, 641–648.PubMedGoogle Scholar
  67. 67.
    Walker, D. G. and McGeer, P. L. (1992) Complement gene expression in human brain: comparison between normal and Alzheimer disease cases, Mol. Brain Res. 14, 106–109.Google Scholar
  68. 68.
    Fischer, B., Schmol, H., Riederer, P., Bauer, J., Platt, D., and Popa-Wagner, A. (1995) Complement Clq and C3 mRNA expression in the frontal cortex of Alzheimer’s patients, J. Mol. Med. 73, 465–471.PubMedGoogle Scholar
  69. 69.
    Tranque, R, Naftolin, F., and Robbins, R. (1994) Differential regulation of astrocyte plasminogen activators by insulin-like growth factor-I and epidermal growth factor, Endocrinology 134, 2606–2613.PubMedGoogle Scholar
  70. 70.
    Barnum, S. R., Jones, J. L., and Benveniste, E. N. (1993) Interleukin-1 and tumor necrosis factor mediated regulation of C3 gene expression in human astroglioma cells, Glia 7, 225–236.PubMedGoogle Scholar
  71. 71.
    McGeer, P. L., Walker, D. G., Akiyama, H., Kawamata, T., Guan, A. L., Parker, C. J., Okada, N., and McGeer, E. G. (1991) Detection of the membrane inhibitor of reactive lysis (CD59) in diseased neurons of Alzheimer brain, Brain Res. 544, 315–319.PubMedGoogle Scholar
  72. 72.
    Choi-Miura, N.-H., Ihara, Y., Fukuchi, K., Takeda, M., Nakano, Y., Tobe, T., and Tomita, M. (1992) SP-40, 40 is a constituent of Alzheimer’s amyloid, Acta Neuropathol. 83, 260–264.PubMedGoogle Scholar
  73. 73.
    May, P. C., Lampert-Etchells, M., Johnson, S. A., Poirier, J., Masters, J. N., and Finch, C. E. (1990) Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer’s disease and in response to experimental lesions in rat, Neuron 5, 831–839.PubMedGoogle Scholar
  74. 74.
    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, 19–28.PubMedGoogle Scholar
  75. 75.
    Tuohy, J. M., Schultz, J. J., Brachova, L., Lue, L.-F., and Rogers, J. (1993) Evidence of increased levels of C4 binding protein in Alzheimer’s disease, Neurosci. Abstr. 19, 834.Google Scholar
  76. 76.
    Walker, D. G., Yasuhara, O., Patston, P.A., McGeer, E. G., and McGeer, R L. (1995) Complement C 1 inhibitor is produced by brain tissue and is cleaved in Alzheimer disease, Brain Res. 675, 75–82.PubMedGoogle Scholar
  77. 77.
    May, P. C. and Finch, C. E. (1992) Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration, Trends Neurosci. 15, 391–396.PubMedGoogle Scholar
  78. 78.
    Wong, R T., McGeer, P. L., and McGeer, E. G. (1992) Decreased prostaglandin synthesis in postmortem cerebral cortex from patients withAzleheimer’s disease, Neurochem. Int. 21, 197–202.PubMedGoogle Scholar
  79. 79.
    de Vries, H. E., Hoogendoorn, K. H., van Dijk, J., Zijlstra, F. J., van Dam, A. M., Breimer, D. D., van Verkel, T. J., de Boer, A. G., and Kuiper, J. (1995) Eicosanoid production by rat cerebral endothelial cells: stimulation by lipopolysaccharide, interleukin-1 and interleukin-6, J. Neuroimmunol. 59, 1–8.PubMedGoogle Scholar
  80. 80.
    Matsuo, M., Hamasaki,Y., Fujiyama, F., and Miyazaki, S. (1995) Eicosanoids are produced by microglia, not by astrocytes, in rat glial cell cultures, Brain Res. 685, 201–204.PubMedGoogle Scholar
  81. 81.
    Colton, C. A. and Gilbert, D. L. (1993) Microglia, an in vivo souce of reactive oxygen species in the brain, Adv. Neurol. 59, 321–326.PubMedGoogle Scholar
  82. 82.
    Brown, G. C., Bolanos, J. P., Heales, S. J. R., and Clark, J. B. (1995) Nitric oxide produced by activated astrocytes rapidly and reversibly inhibits cellular respiration, Neurosci. Lett. 193, 201–104.PubMedGoogle Scholar
  83. 83.
    Akiyama, H., Ikeda, K., Kondo, H., and McGeer, P. L. (1992) Thrombin accumulation in brains of patients with Alzheimer’s disease, Neurosci. Lett. 146, 152–154.PubMedGoogle Scholar
  84. 84.
    Weinstein, J. R., Gold, S. J. Cunningham, D. D., and Gall, C. M. (1995) Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA, J. Neurosci. 15, 2906–2919.Google Scholar
  85. 85.
    Kalaria, R. N., Golde, T., Kroon, S. N., and Perry, G. (1993) Serine protease inhibitor antithrombin III and its messenger RNA in the pathogenesis of Alzheimer’s disease, Am. J. Pathol. 143, 886–893.PubMedGoogle Scholar
  86. 86.
    McComb, R. D., Miller, K. A., and Carson, S. D. (1991) Tissue factor antigen in senile plaques of Alzheimer’s disease, Am. J. Pathol. 139, 491–494.PubMedGoogle Scholar
  87. 87.
    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, 234–240.PubMedGoogle Scholar
  88. 88.
    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 2macroglobulin receptor/low-density-lipoprotein receptor-related protein, Ann. Neurol. 37, 211–217.Google Scholar
  89. 89.
    Nakajima, K., Tsuzaki, N., Shimojo, M., Hamanoue, M., and Kohsaka, S. (1992) Microglia isolated from rat brain secrete a urokinase-type plasminogen activator, Brain Res. 577, 285–292.PubMedGoogle Scholar
  90. 90.
    Reddington, M., Hass, C., and Kreutzlberg, G. W. (1994) The plasminogen activator system in neurons and glia during motoneuron regeneration, Neuropathol. Appl. Neurobiol. 20, 188–190.PubMedGoogle Scholar
  91. 91.
    Akiyama, H., Ideda, K., Kondo, H., Kato, M., McGeer, E. G., and McGeer, P. L. (1993) Microglia express the type 2 plasminogen activator inhibitor in the brain of control subjects and patients with Alzheimer’s disease, Neurosci. Lett. 164, 233–235.PubMedGoogle Scholar
  92. 92.
    Choi, B. H., Suzuki, M., Kim, T., Wagner, S. L., and Cunningham, D. D. (1990) Protease nexin-1. Localization in the human brain suggests a protective role against extravasated serine proteases, Am. J. Pathol. 137, 741–747.PubMedGoogle Scholar
  93. 93.
    Wagner, S. L., Geddes, J. W., Cobnan, C. W., Lau, A. L., Gurwitz, D., Isackson, R J., and Cunningham, D. D. (1989) Protease nexin-1 an antithrombin with neurite outgrowth activity, is reduced in Alzheimer’s disease, Proc. Natl. Acad. Sci. USA 86, 8284–8288.PubMedGoogle Scholar
  94. 94.
    Nakajima, K., Tsuzaki, N., Takemoto, N., and Kohsaka, S. (1992) Production and secretion of plasminogen in cultured rat brain Microglia, FEBS Lett. 308, 179–182.PubMedGoogle Scholar
  95. 95.
    Dihanich, M., Kaser, M., Reinhard, E., Cunningham, D. D., and Monard, D. (1991) Pro-thrombin mRNA is expressed by cells of the nervous system, Neuron 6, 575–581.PubMedGoogle Scholar
  96. 96.
    Yamamoto, M., Sawaya, R., Mohanam, S., Loskutoff, D. J., Bruner, J. M., Rao, V. H., Oka, K., Tomonaga, M., Nicolson, G. L., and Rao, J. S. (1994) Expression and cellular localization of messenger RNA for plasminogen activator inhibitor type I in human astrocytomas in vivo, Cancer Res. 54, 3329–3332.PubMedGoogle Scholar
  97. 97.
    Dent, M. A., Sumi, Y., Morris, R. J., and Seeley, P. J. (1993) Urokinase-type plasminogen activator expression by neurons and oligodendrocytes during process outgrowth in developing rat brain, Eur. J. Neurosci. 5, 633–647.PubMedGoogle Scholar
  98. 98.
    Frohman, E. M., Frohman, T. C., Gupta, S., de Fougerolles, A., and van den Noort, E. (1991) Expression of intercellular adhesion molecule-1 (ICAM-1) in Alzheimer’s disease, J. Neurol. Sci. 106, 105–111.PubMedGoogle Scholar
  99. 99.
    Verbeek, M. M., Otte-Holler, I., Westphal, J. R., Wesseling, P., Ruiter, D. J., and de Waal, R. M. W. (1994) Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer’s disease, Am. J. Pathol. 144, 104–116.PubMedGoogle Scholar
  100. 100.
    Satoh, J., Kim, S. U., Kastrukoff, L. F., and Takei, F. (1991) Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes, J. Neurosci. Res. 29, 1–12.PubMedGoogle Scholar
  101. 101.
    Gillian, A. M., Brion, J.-P., and Breen, K. C. (1994) Expression of the neural cell adhesion molecule (NCAM) in Alzheimer’s disease, Neurodegen. 3, 283–291.Google Scholar
  102. 102.
    Rozemuller, J. M., Eikelenboom, P., Pals, S. T., and Stam, F. C. (1989) Microglial cells around amyloid plaques in Alzheimer’s disease express leucocyte adhesion molecules of the LFA-1 family, Neurosci. Lett. 101, 228–292.Google Scholar
  103. 103.
    Akiyama, H., Tooyama, I., Kondo, H., Ideda, K., Kimura, H., McGeer, E. G., and McGeer, P. L. (1994) Early response of brain resident microglia to kainic acid-induced hippocampal lesions, Brain Res. 635, 257–268.PubMedGoogle Scholar
  104. 104.
    Rosenman, S. J., Shrikant, P., Dubb, L., Benveniste, E. N., and Ransohoff, R. M. (1995) Cytokine-induced gene expression of vascular cell adhesion molecule-1 (VCAM-1) in astrocytes and astrocytoma cell lines, J. Immunol. 154, 1888–1899.PubMedGoogle Scholar
  105. 105.
    McGeer, P. L., McGeer, E. G., Itagaki, S., and Mizukawa, K. (1987) Anatomy and pathology of the basal ganglia, Can. J. Neurol. Sci. 12, 363–372.Google Scholar
  106. 106.
    Akiyama, H., Nishimura, T., Kondo, H., Ikeda, K., Hayashi, V., 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, 171–174.PubMedGoogle Scholar
  107. 107.
    Tomozawa, Y., Inoue, T., and Satoh, M. (1995) Expression of type I interleukin-1 receptor mRNA and its regulation in cultured astrocytes, Neurosci. Lett. 195, 57–60.PubMedGoogle Scholar
  108. 108.
    Eizenberg, O., Faberelman, A., Lotan, M., and Schwartz, M. (1995) Interleukin-2 transcripts in human and rodent brains—possible expression by astrocytes, J. Neurochem. 64, 1928–1936.PubMedGoogle Scholar
  109. 109.
    Sawada, M., Suzumura, A., and Marunouchi, T. (1995) Induction of functional interleukin-2 receptor in mouse microglia, J. Neurochem. 64, 1973–1979.PubMedGoogle Scholar
  110. 110.
    Akiyama, H. and McGeer, P. L. (1990) Brain microglia constituvely express b-2 integrins, J. Neuroimmunol. 30, 81–93.PubMedGoogle Scholar
  111. 111.
    V, E. G., and McGeer, P. L. (1994) Expression of MRP 14, 27E 10, interferon-alpha and leucocyte common antigen by reactive microglia in postmortem human brain tissue, J. Neuroimmunol. 50, 195–201.Google Scholar
  112. 112.
    Rogers, J. and Rovigatti, U. (1988) Immunologic and tissue culture approaches to the neurobiology of aging, Neurobiol. Aging 9, 759–762.PubMedGoogle Scholar
  113. 113.
    Fraser, P. E., Nguyen, J. T., McLachlan, D. R., Abraham, C. R., and Kirschner, D. A. (1993) al-Antichymotrypsin binding to Alzheimer Ab peptides is sequence specific and induces fibril disaggregation in vitro, J. Neurochem. 61, 298–305.Google Scholar
  114. 114.
    Ma, J., Yee, A., Brewer, H. B., Das, S., and Potter, H. (1994) Amyloid-associated proteins a1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer 0-protein into filaments, Nature 372, 92–94.Google Scholar
  115. 115.
    Hamazaki, H. (1995) Amyloid P component promotes aggregation of Alzheimer’s beta-amyloid peptide, Biochem. Biophys. Res. Commun. 211, 349–353.PubMedGoogle Scholar
  116. 116.
    Tennent, G. A., Loyal, L. B., and Pepys, M. B. (1995) Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis, Proc. Natl. Acad. Sci. USA 92, 4299–4303.PubMedGoogle Scholar
  117. 117.
    Koller, M., Hensler, T., Konig, B., Prevost, G., Alouf, J., and Konig, W. (1993) Induction of heat-shock proteins by bacterial toxins, lipid mediators and cytokines in human leukocytes, Infect. Dis. 278, 365–376.Google Scholar
  118. 118.
    Buxbaum, J. D., Oishi, M., Chen, H. I., Pinkas-Kramarski, R., Jaffe, E. A., Gandy, S. E., and Greengard, P. (1992) Cholinergic agonists and interleukin-1 regulate processing and secretion of the Alzheimer b/A4 amyloid protein precursor, Proc. Natl. Acad. Sci. USA 89, 10075–10078.PubMedGoogle Scholar
  119. 119.
    Forloni, G., Demicheli, F., Giorgi, S., Bendotti, C., and Angeretti, N. (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
  120. 120.
    Goldgaber, D., Harris, H. W., Hla, T., Maciag, T., Donnelly, R. J., Jacobsen, J. S., Vitek, M. P., and Gajdusek, C. (1989) Interleukin-1 regulates synthesis of amyloid 0-protein precursor mRNA in human endothelial cells, Proc. Natl. Acad. Sci. USA 86, 7606–7610.PubMedGoogle Scholar
  121. 121.
    Gray, C. W. and Patel, A. J. (1993) Regulation of 13-amyloid precursor protein isoform mRNAs by transforming growth factor-bl and interleukin-lb in astrocytes, Mol. Brain Res. 19, 251–256.PubMedGoogle Scholar
  122. 122.
    Araujo, D. M. and Cotman, C. W. (1992) ß-Amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer’s disease, Brain Res. 569, 141–145.PubMedGoogle Scholar
  123. 123.
    Brachova, L., Lue, L.-F., Byttner, S., Sue, L., Civin, W. H., Schultz, J., Tuohy, J., and Rogers, J. (1993) Reduced complement activation in nondemented patients with excessive 13-amyloid peptide deposition, Neurosci. Abst. 19, 833.Google Scholar
  124. 124.
    Webster, S., Glabe, C., and Rogers, J. (1995) Multivalent binding of complement protein Clq to the amyloid 13-peptide promotes the nucleation phase of Ab aggregation, Biochem. Biophys. Res. Commun. 217, 869–875.PubMedGoogle Scholar
  125. 125.
    Webster, S., O’Barr, S., and Rogers, J. (1994) Enhanced aggregation and 13 structure of amyloid b peptide after co-incubation with Clq, J. Neurosci. Res. 39, 448–456.PubMedGoogle Scholar
  126. 126.
    Webster, S. and Rogers, J. (1996) Relative efficacies of amyloid b peptide (Ab) binding proteins in Ab aggregation, J. Neurosci. Res. submitted for publication.Google Scholar
  127. 127.
    Jiang, H., Burdick, D., Glabe, C. G., Cotman, C. W., and Tenner, A. J. (1994) 13-amyloid activates complement by binding to a specific region of the collagen-like domain of the Clq chain, J. Immunol. 152, 5050–5059.Google Scholar
  128. 128.
    Jiang, H., Robey, F. A., and Gewurz, H. (1992) Localization of sites through which C-reactive protein binds and activates compleme:nt to residues 14–26 and 76–92 of the human Clq A chain, J. Exp. Med. 175, 1373–1379.PubMedGoogle Scholar
  129. 129.
    Pike, C. J., Walencewicz, A. J., Glabe, C. G., and Cotman, C. W. (1991) In vitro aging of ßamyloid protein causes peptide aggregation and neurotoxicity, Brain Res. 56, 311–314.Google Scholar
  130. 130.
    Schultz, J., Schaller, J., McKinley, M., Bradt, B., Cooper, N., May, P., and Rogers, J. (1994) Enhanced cytotoxicity of amyloid b-peptide by a complement dependent mechanism, Neurosci. Lett. 175, 99–102.PubMedGoogle Scholar
  131. 131.
    Yankner, B. A., Duffy, L. K., and Kirschner, D. A. (1990) Neurotrophic and neurotoxic effects of amyloid-beta protein: Reversal by tachykinin neuropeptides, Science 250, 279–282.PubMedGoogle Scholar
  132. 132.
    Cooper, N. R. (1985) The classical complement pathway: activation and regulation of the first complement component, Adv. Immunol. 37, 151–157.PubMedGoogle Scholar
  133. 133.
    Meri, S., Morgan, B. P., Davies, A., Daniels, R. H., Olavesen, M. G., Waldman, H., and Lachmann, P. J. (1990) Human protectin (CD59), an 18,000–20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bylayers, Immunology 71, 1–9.Google Scholar
  134. 134.
    Oda, T., Wals, P., Osterburg, H. H., Johnson, S.A., Pasinetti, G. M., Morgan, T. E., Rozovsky, I., Stine, W. B., Snyder, S. W., and Holzman, T. F. (1995) Clusterin (apoJ) alters the aggre-gation of amyloid beta-peptide (A beta 1–42) and forms slowly sedimenting A beta complexes that cause oxidative stress, Exp. Neurol. 136, 22–31.Google Scholar
  135. 135.
    Ross, G. D. and Vetvicka, V. (1993) CR3 (CD 1l b, CD 18) a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions, Clin. Exp. Immunol. 92, 181–184.PubMedGoogle Scholar
  136. 136.
    Myllykangas-Luosujarvi, R., and Isomaki, H. (1994) Alzheimer’s disease and rheumatoid arthritis, Br. J. Rheumatol. 33, 501–502.PubMedGoogle Scholar
  137. 137.
    Kinouchi, T., Ono, Y., Sorimachi, H., Ishiura, S., and Suzuki, K. (1995) Arachidonate metablites affect the secretion of an N-termal fragment of Alzheimer’s disease amyloid percursor protein, Biochem. Biophys. Res. Comm. 209, 841–849.PubMedGoogle Scholar
  138. 138.
    Jalink, K. and Moolenaar, W. H. (1992) Thrombin receptor activation causes rapid neural cell rounding and neurite retraction independent of classic second messengers, J. Cell. Biol. 118, 411–419.PubMedGoogle Scholar
  139. 139.
    Masliah, E., Mallory, M., Hansen, L., Alford, M., Albright, T., DeTeresa, R., Terry, R., Baudier, J., and Saitoh, T. (1991) Patterns of aberrant sprouting in Alzheimer’s Disease, Neuron 6, 729–739.PubMedGoogle Scholar
  140. 140.
    Nagata, K., Nakajima, K., Takemoto, N., Saito, H., and Kohsaka, S. (1993) Microglia-derived plasminogen enhances neunte outgrowth from explant cultures of rat brain, Int. J. Dey. Neurosci. 11, 227–237.Google Scholar
  141. 141.
    Andersen, K., Launer, L. J., Ott, A., Hoes, A. W., Breteler, M. M. B., and Hofman, A. (1995) Do nonsteroidal antiinflammatory drugs decrease the risk for Alzheimer’s disease? Neurology 45, 1441–1445.PubMedGoogle Scholar
  142. 142.
    Breitner, J. C. S., Gau, B. A., Welsh, K. A., Plassman, B. L., McDonald, W. M., Helmas, M. J., and Anthony, J. C. (1994) Inverse association of anti-inflammatory treatments and Alzheimer’s disease, Neurology 44, 227–232.PubMedGoogle Scholar
  143. 143.
    Breitner, J. C. S., Welsh, K. A., Helms, M. J., Gaskell, P. C., Gau, B. A., Roses, A. D., Pericak-Vance, M. A., and Saunders, A. M. (1995) Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs, Neurobiol. Aging 16, 520–523.Google Scholar
  144. 144.
    Broe, G. A., Henderson, A. S., Creasey, H., McCusker, E., Korten, H. E., Jorm, A. F., Longley, W., and Anthony, J. C. (1990) A case-control study of Alzheimer’s disease in Australia, Neurology 40, 1698–1707.PubMedGoogle Scholar
  145. 145.
    Canadian Study of Health and Aging (1994) Risk factors for Alzheimer’s disease in Canada, Neurology 44, 2073–2080.Google Scholar
  146. 146.
    Graves, A. B., White, E., Koepsell, T. D., Reifler, B. V., van Belle, G., Larson, E. B., and Raskind, M. (1990) A case-control study of Alzheimer’s disease, Ann. Neurol. 28, 766–774.PubMedGoogle Scholar
  147. 147.
    Jenkinson, M. I., Bliss, M. R., Brain, A. T., and Scott, D. L. (1989) Rheumatoid arthritis and senile dementia of the Alzheimer’s type, Br. J. Rheumatol. 28, 86–87.PubMedGoogle Scholar
  148. 148.
    Li, G., Shen, Y. C., Chen, C. H., Zhau, Y. W., and Silverman, J. M. (1992) A case-control study of Alzheimer’s disease in China, Neurology 42, 1481–1482.PubMedGoogle Scholar
  149. 149.
    Lucca, U., Tettamanti, M., Forloni, G., and Spagnoli, A. (1994) Nonsteroidal antiinflammatory drug use in Alzheimer’s disease, Biol. Psychiatry 36, 854–856.PubMedGoogle Scholar
  150. 150.
    McGeer, P. L., Harada, N., Kimura, H., McGeer, E. G., and Schulzer, M. (1992) Prevalence of dementia amongst elderly Japanese with leprosy: apparent effect of chronic drug therapy, Dementia 3, 146–149.Google Scholar
  151. 151.
    McGeer, R L., McGeer, E. G., Rogers, J., and Sibley, J. (1990) Anti-inflammatory drugs and Alzheimer’s disease, Lancet 335, 10–37.Google Scholar
  152. 152.
    Rich, J. B., Rasmusson, D. X., Folstein, M. F., Carson, K. A., Kawas, C., and Brandt, J. (1995) Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease, Neurology 45, 51–55.PubMedGoogle Scholar
  153. 153.
    Rogers, J., Kirby, L. C., Hempelman, S. R., Berry, D. L., McGeer, P. L., Kaszniak, A. W., Zalinski, J., Cofield, M., Mansukhani, L., Willson, P., and Kogan, F. (1993) Clinical trial of indomethacin in Alzheimer’s disease, Neurology 43, 1609–1611.PubMedGoogle Scholar
  154. 154.
    Lue, L.-F., Brachova, L., Walker, D. G., and Rogers, J. (1996) Characterization of glial cultures from rapid autopsies of Alzheimer’s and control patients, Neurobiol. Aging, 17, 421–429.PubMedGoogle Scholar
  155. 155.
    Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein, Nature 373, 523–527.PubMedGoogle Scholar
  156. 156.
    Gitter, B. D., Cox, L. M., Keith, P. T., Rydel, R. E., and May, P. C. (1993) Amyloid beta peptide (Aß) potentiates cytokine secretion by interleukin-lß activated human astrocytoma cells, Neurosci. Abstr. 19, 832.Google Scholar

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© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Joseph Rogers
  • Stephen O’Barr

There are no affiliations available

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