Elucidating Molecular Mechanisms of Alzheimer’s Disease in Microglial Cultures

  • J. Rogers
  • L.-F. Lue
  • D. G. Walker
  • S. D. Yan
  • D. Stern
  • R. Strohmeyer
  • C. J. Kovelowski
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 39)

Abstract

Particularly in the context of innate inflammatory mechanisms, micro-glia appear to play important roles in a wide range of neurodegenerative diseases, including multiple sclerosis, Parkinson’s disease, and human immunodeficiency virus (HIV)-associated dementia (reviewed in Banati et al. 1993; Dickson et al. 1993; McGeer et al. 1993). It should not be surprising, then, that microglial activation has been found to be a crucial event mediating inflammatory responses in Alzheimer’s disease (AD) (reviewed in Neuroinflammation Working Group 2000).

Keywords

Migration Dementia Trypsin Beach Neurol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ard MD, Cole GM, Wei J, Mehrie AP, Fratkin JD (1996) Scavenging of Alzheimer’s amyloid beta-protein by microglia in culture. J Neurosci Res 43: 190–192PubMedCrossRefGoogle Scholar
  2. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7: 111–118PubMedCrossRefGoogle Scholar
  3. Bard F, Cannon C, Barbour R, Burke RL, Games L, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Lieberburg I, Motter R, Nguyen M, Soriano F, Vasquez N, Weiss K, Welch B, Seubert P, Schenk D, Yednock T (2000) Peripherally administered antibodies against amyloid 13-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6: 916–919PubMedCrossRefGoogle Scholar
  4. Brachova L, Lue, L-F, Schultz J, El Rashidy T, Rogers J (1993) Association cortex, cerebellum, and serum concentrations of C1Q and factor B in Alzheimer’s disease. Mol. Brain Res 18: 329–334Google Scholar
  5. Canning DR, Mckeon RJ, DeWitt DA, Perry G, Wujek JR, Frederickson RC, Silver J (1993) beta-Amyloid of Alzheimer’s disease induces reactive gliosis that inhibits axonal outgrowth. Exp Neurol 124: 289–98Google Scholar
  6. Cotter RL, Burke WJ, Thomas VS, Potter JF, Zheng J, Gendelman HE (1999) Insights into the neurodegenerative process of Alzheimer’s disease: a role for mononuclear phagocyte-associated inflammation an d neurotoxicity. J Leukoc Biol 65: 416–427PubMedGoogle Scholar
  7. Davis, J.B, McMurray HF, Schubert D (1992) The amyloid beta-protein of Alzheimer’s disease is chemotactic for mononuclear phagocytes. Biochem Biophys Res Commun 189: 1096–1100PubMedCrossRefGoogle Scholar
  8. DeGroot CJA, Montagne L, Janssen I, Ravid R, Van Der Valk P, Veerhuis R (2000) Isolation and characterization of adult microglial cells and oligodendrocytes Derived from postmortem human brain tissue. Brain Res Proto 5: 585–594Google Scholar
  9. Dickson DW, Lee SC, Mattiace LA, Yen SHC, Brosnan C (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer’s disease. Glia 7: 75–83PubMedCrossRefGoogle Scholar
  10. Edwards SW, Watson F, Gasmi L, Moulding DA, Quayle JA (1997) Activation of human neutrophils by soluble immune complexes: role of Fc gamma RII and Fc gamma R III b in stimulation of the respiratory burst and elevation of intracellular Cat+. Ann NY Acad Sci 832: 341–357PubMedCrossRefGoogle Scholar
  11. El Khoury J, Hickman SE, Thomas CA, Cao L, Silverstein SC, Loike JD (1996) Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 382: 716–719PubMedCrossRefGoogle Scholar
  12. Fiala M, Zhang L, Gan Z, Sherry B, Taub D, Graves MC, Hama S, Way D, Weinand M, Witte M, Lorton D, Duo Y-M, Roher AE (1998) Amyloid-ß induces chemokine secretion and monocyte migration across a human blood-brain barrier model. Mol Med 4: 480–489PubMedGoogle Scholar
  13. Frautschy SA, Cole GM, Baird A (1992) Phagocytosis and deposition of vascular beta-amyloid in rat brains injected with Alzheimer beta-amyloid. Am J Pathol 140: 1389–1399PubMedGoogle Scholar
  14. Frautschy SA, Fusheng Y, Irrizarry M, Hyman B, Saido TC, Hsiao K, Cole GM (1998) Microglial response to amyloid plaques in APPsW transgenic mice. Am J Path 152: 307–317PubMedGoogle Scholar
  15. Gehrmann J, Banati RB, Kreutzberg GW (1993) Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules. J Neuroimmunol 48: 189–198PubMedCrossRefGoogle Scholar
  16. Giulian D, Baker TJ (1986) Characterization of amoeboid microglia isolated from developing mammalian brain. J Neurosci 6: 21–28Google Scholar
  17. Giulian D, Haverkamp LJ, Yu J, Karshin W, Tom D, Li J, Kazanskaia, Kirkpatrick JB, Roher AE (1998) The HHQK domain of beta-amyloid provides a structural basis for the immunopathology of Alzheimer’s disease. J Biol Chem 273: 29719–29726PubMedCrossRefGoogle Scholar
  18. Huang F, Buttini M, Wyss-Coray T, McConlogue L, Kodama T, Pitas RE, Mucke L (1999) Elimination of the class A scavenger receptor does not affect amyloid plaque formation or neurodegeneration in transgenic mice expressing human amyloid protein precursors. Am J Pathol 155: 1741–1747PubMedCrossRefGoogle Scholar
  19. Hulette CM, Downey BT, Burger PC (1992) Macrophage markers in diagnostic neuropathology. Am J Surg Pathol 16: 493–499PubMedCrossRefGoogle Scholar
  20. Ishizuka K, Kimura T, Igata-yi R, Katsuragi S, Takamatsu J, Miyakawa T (1997) Identification of monocyte chemoattractant protein-1 in senile plaques and reactive microglia of Alzheimer’s disease. Psych Clin Neurosci 51: 135–138CrossRefGoogle Scholar
  21. Janus C, Pearson J, McLaurin J, Mathews PM, Jiang Y, Schmidt SD, Chishti MA, Horne P, Heslin D, French J, Mount HT, Nixon RA, Mercken M, Bergeron C, Fraser PE, St George-Hyslop P, Westaway D (2000) Aß peptide immunization reduces behavioral impairment and plaques in a mouse model of Alzheimer’s disease. Nature 408: 979–982PubMedCrossRefGoogle Scholar
  22. Kim Su, Sato Y, Silberberg DH, Pleasure DE, Rorke LB (1983) Long-term culture of human oligodendrocytes. J Neurol Sci 62: 295–301PubMedCrossRefGoogle Scholar
  23. Kuo Y-M, Kokjohn TA, Beach TG, Sue LI, Brune D, Lopez JC, Kalback WM, Abramowski D, Sturchler-Pierrat C, Staufenbiel M, Roher AE (2001) Comparative analysis of amyloid 13 chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer’s disease brains. J Biol Chem 276: 12991–12998PubMedCrossRefGoogle Scholar
  24. Lee SC, Liu W, Brosnan CF, Dickson DW (1992) Characterization of primary human fetal dissociated central nervous system cultures with an emphasis on microglia. Lab Investig 67: 465–476PubMedGoogle Scholar
  25. Ling EA, Wong WC (1993) The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 7: 10–18CrossRefGoogle Scholar
  26. Lisak R, Pleasure D, Manning M, Saida T (1981) Long-term culture of bovine oligodendroglia isolated with a Percoll gradient. Brain Res 113: 165–170Google Scholar
  27. Lorton D (1997) (3-amyloid-induced IL-113 release from an activated human monocyte cell line is calcium-and G-protein-dependant. Mech Aging Dev 94:119–122Google Scholar
  28. Lorton D, Schaller J, Lala A, De Nardin E (2000) Chemotactic-like receptors and Abeta peptide induced responses in Alzheimer’s disease. Neurobiol Aging 21: 463–473PubMedCrossRefGoogle Scholar
  29. Lue LF, Brachova L, Civin WH, Rogers J (1996a) Inflammation, AB deposition, and neurofibrillary tangle formation as correlates of Alzheimer’s disease neurodegeneration. J Neuropathol Exp Neurol 55: 1083–1088Google Scholar
  30. Lue LF, Brachova L, Walker DG, Rogers J (1996b) Characterization of glial cultures from rapid autopsies of Alzheimer’s and control patients. Neurobiol Aging 17: 421–429PubMedCrossRefGoogle Scholar
  31. Lue LF, Rydel R, Brigham EF, Yang LB, Hampel H, Murphy Jr. GM, Brachova L,Yan SD, Walker DG, Shen Y, Rogers J (2002a) Inflammatory repertoire of Alzheimer’s disease and non-demented elderly microglia in vitro. Glia (in press)Google Scholar
  32. Lue LF, Walker DG, Brachova L, Beach TG, Rogers J. Schmidt AM, Stern D, Yan SD (2002b) Microglial receptor for advanced glycation endproductsGoogle Scholar
  33. RAGE) in Alzheimer’s disease: identification of cellular activation mechanism. Exp Neurol (in press)Google Scholar
  34. McGeer P, Kawamata T, Walker DG, Akiyama H, Tooyama I, McGeer EG (1993) Microglia in degenerative neurological disease. Glia 7: 84–92PubMedCrossRefGoogle Scholar
  35. Meda L, Bonaiuto C, Szendrei GI, Ceska M, Rossi F, Cassatella MA (1995a) Beta-amyloid (25–35) induces the production of interleukin-8 from human monocytes. J Neuroimmunol 59: 29–33PubMedCrossRefGoogle Scholar
  36. Meda L, Baron P, Prat E, Scarpini E, Scarlato G, Cassatella MA, Rossi F (1999) Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with beta-amyloid. J Neuroimmunol 93: 4–52CrossRefGoogle Scholar
  37. Meda L, Cassatella MA, Szendrei GI, Otvos L, Baron P, Villalba M, Ferrari D, Rossi F (1995b) Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 374: 647–650PubMedCrossRefGoogle Scholar
  38. Meda L, Bernaconi S, Bonaiuto C, Sozzani S, Zhou D, Otvos L, Mantovani A, Rossi F, Cassatella MA (1996) Beta-amyloid (25–35) peptide and IFNgamma synergistically induce the production of the chemotactic cytokine MCP-1/JE in monocytes and microglial cells. J Immunol 157: 1213–1218PubMedGoogle Scholar
  39. Morgan D, Diamond DM, Gottschall PE, Ugen KE, Dickey C, Hardy J, Duff K, Jantzen P, DiCarlo G, Wilcock D, Connor K, Hatcher J, Hope C, Gordon M, Arendash GW (2000) A13 peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature 408: 982–985PubMedCrossRefGoogle Scholar
  40. Nakai M, Hojo K, Taniguchi T, Terashima A, Kawamata T, Hashimoto T, Maeda K, Tanaka C (1998) PKC and tyrosine kinase involvement in amyloid beta (25–35)-induced chemotaxis of microglia. NeuroReport 9: 3467–3470PubMedCrossRefGoogle Scholar
  41. Neuroinflammation Working Group (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21: 383–421Google Scholar
  42. Paresce DM, Chung H, Maxfield FR (1997) Slow degradation of aggregates of the Alzheimer’s disease amyloid beta-protein by microglial cells. J Biol Chem 29390–29397Google Scholar
  43. Peress NS, Fleit HB, Perillo E, Kuljis R, Pezzullo C (1993) Identification of FcyRI, II and III on normal human brain ramified microglia and on micro-glia in senile plaques in Alzheimer’s disease. J Neuroimmunol 48: 71–80Google Scholar
  44. Perlmutter LS, Barron E, Chui HC (1990) Morphologic association between microglia senile plaque amyloid in Alzheimer’s disease. Neurosci Lett 119: 32–36PubMedCrossRefGoogle Scholar
  45. Peterson PK, Hu S, Salak-Johnson J, Molitor TW, Chao CC (1997) Differential production of and migratory response to B chemokines by human microglia and astrocytes. J Infect Dis 175: 478–481PubMedCrossRefGoogle Scholar
  46. Raley MJ, Lennartz MR, Loegering DJ (1999) A phagocytic challenge with IgG-coated erythrocytes depresses macrophage respiratory burst and phagocytic function by different mechanisms. J Leukoc Biol 66: 803–806PubMedGoogle Scholar
  47. Rogers J, Lue LF (2001) Microglial chemotaxis, activation, and phagocytosis of amyloid ß peptide as linked phenomena in Alzheimer’s disease. Interntl J Neurochem (in press)Google Scholar
  48. Rogers J, Luber-Narod J, Styren Sd, Civin WH (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: 339–349PubMedCrossRefGoogle Scholar
  49. Rogers J, Cooper NR, Schultz J, McGeer PL, Webster S, Styren SD, Civin WH, Brachova L, Bradt B, Ward P, Lieberburg I (1992) Complement activation by f3-amyloid in Alzheimer’s disease. Proc Nat Acad Sci (USA) 89: 10016–10020CrossRefGoogle Scholar
  50. Rozovsky I, Finch CE, Morgan TE (1998) Age-related activation of microglia and astrocytes: In vitro studies show persistent phenotypes of aging, increased proliferation, and resistance to down-regulation. Neurobiol Aging 19: 97–103Google Scholar
  51. Schenk D, Borbour R, Dunn W, et al (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400: 173–177PubMedCrossRefGoogle Scholar
  52. Stoltzner SE, Grenfell TJ, Mori C, Wisniewski KE, Wisniewski TM, Selkoe DJ, Lemere C (2000) Temporal accrual of complement proteins in amyloid plaques in Down’s syndrome with Alzheimer’s disease. Am J Pathol 156: 488–499CrossRefGoogle Scholar
  53. Sutterwala FS, Noel GJ, Salgame P, Mosser DM (1998) Reversal of proinflammatory responses by ligating the macrophage Fc gamma receptor type I. J Exp Med 188: 217–222PubMedCrossRefGoogle Scholar
  54. Tomozawa Y, Inoue T, Takahashi M, Adachi M, Satoh M (1996) Apoptosis of culturedmicroglia by the deprivation of macrophage colony-stimulating factor. Neurosci Res 25: 7–15PubMedCrossRefGoogle Scholar
  55. Turrin NP, Plata-Salaman CR (2000) Cytokine-cytokine interactions and the brain. Brain Res Bulletin 51: 3–9CrossRefGoogle Scholar
  56. Ulvestad E, Williams K, Bjerkvig R, Tiekotter K, Antel J, Matre R (1994a) Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells. J Leukoc Biol 56: 732–740PubMedGoogle Scholar
  57. Ulvestad E, Williams K, Matre R, Nyland H, Olivier A, Antel J (1994b) Fc receptors for IgG on cultured human microglia mediate cytotoxicity and phagocytosis of antibody-coated targets. J Neuropathol Exp Neuro 53: 27–36CrossRefGoogle Scholar
  58. Veerhuis R, Janssen I, De Groot CJA, Van Muiswinkel FL, Hack CE, Eikelenboom P (1999) Cytokines associated with amyloid plaques in Alzheimer’s disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not Cl-inhibitor. Exp Neurol 160: 289–299PubMedCrossRefGoogle Scholar
  59. Walker DG, Kim SU, McGeer PL (1995) Complement and cytokine gene expression in cultured microglia derived from postmortem human brains. J Neurosci Res 40: 478–493PubMedCrossRefGoogle Scholar
  60. Webster S, Rogers J (1996) Relative efficacies of amyloid (3 peptide binding proteins in A(3 aggregation. J Neurosci Res 46: 58–66PubMedCrossRefGoogle Scholar
  61. Webster S, Bonnell B, Rogers J (1997a) Charge based binding of complement component Clq to the Alzheimer amyloid 13 peptide. Am J Pathol 150: 1531–1536PubMedGoogle Scholar
  62. Webster S, Bradt B, Rogers J, Cooper NR (1997b) Aggregation state-dependent activation of the classical complement pathway by the amyloid [3 peptide. J Neurochem 69: 388–398PubMedCrossRefGoogle Scholar
  63. Webster S, Lue L-F, Brachova L, Tenner A, McGeer PL, Walker D, Bradt B, Cooper NR, Rogers J (1997c) Molecular and cellular characterizaiton of the membrane attack complex, C5b-9, in Alzheimer’s disease. Neurobiol Aging 18: 415–421Google Scholar
  64. Webster SD, Tenner AJ, Poulos TL, Cribbs DH (1999) The mouse Clq Achain sequence alters beta-amyloid-induced complement activation. Neurobiol Aging 20: 297–304PubMedCrossRefGoogle Scholar
  65. Whittemore SR, Sanon HR, Wood PM (1993) Concurrent isolation and characterization of oligodendrocytes, microglia and astrocytes from adult human spinal cord. Int J Dev Neurosci 11: 755–764PubMedCrossRefGoogle Scholar
  66. Williams K, Bar-Or A, Ulvestad E, Olivier A, Antel J, Yong VW (1992) Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes. J Neuropathol Exp Neurol 51: 538–549PubMedCrossRefGoogle Scholar
  67. Wujek JR, Dority MD, Frederickson RC, Brunden KR (1996) Deposits of A beta fibrils are not toxic to cortical and hippocampal neurons in vitro. Neurobiol Aging 17: 107–113PubMedCrossRefGoogle Scholar
  68. Xia MQ, Hyman BT (1999) Chemokines/chemokinereceptors in the central nervous system and Alzheimer’s disease. J Neurovirol 5: 32–41PubMedCrossRefGoogle Scholar
  69. Yan SD, Roher A, Schmidt AM, Stern DM (1999) Cellular cofactors for amyloid (3-peptide-induced cell stress: moving from cell cultures to in vivo. Am J Pathol 155: 1403–1410PubMedCrossRefGoogle Scholar
  70. Yan SD, Roher A, Chaney M, Zlokovic B, Schmidt AM, Stern D (2000) Cellular cofactors potentiating induction of stress and cytotoxicity by amyloid beta-peptide. Biochim Biophys Acta 1502: 145–157PubMedCrossRefGoogle Scholar
  71. Yan SD, Zhu H, Fu J, Yan SF, Roher, Tourtellotte WW, Ragavashisth T, Chen X, Godman GC, Stern D, Schmidt AM (1997) Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expresGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • J. Rogers
  • L.-F. Lue
  • D. G. Walker
  • S. D. Yan
  • D. Stern
  • R. Strohmeyer
  • C. J. Kovelowski

There are no affiliations available

Personalised recommendations