Advertisement

Inflammatory Pathways

Implications in Alzheimer’s Disease
  • W. Sue T. Griffin
  • Jin G. Sheng
  • Robert E. Mrak
Part of the Contemporary Neuroscience book series (CNEURO)

Abstract

Alzheimer’s disease (AD) is a dementing illness characterized clinically by global intellectual decline and pathologically by a profusion of microscopic brain lesions containing extracellular amyloid in a β-pleated sheet conformation (β-amyloid) associated with abnormal (dystrophic) neuntes. These neuritic β-amyloid plaques are thought to originate as otherwise undistinguished deposits of amyloid protein—diffuse nonneuritic plaques. With condensation of this amyloid, accompanied by the appearance of dystrophic neurites, these amyloid deposits evolve into neuritic plaques containing both diffuse amyloid and β-amyloid (diffuse neuritic plaques). With further evolution, amyloid condenses into a central compact core of β-amyloid within the larger deposit of diffuse amyloid, yielding a dense core neuritic plaque. Continued condensation apparently is accompanied by a loss of associated diffuse amyloid as well as neuritic elements, yielding a dense core of β-amyloid. These dense core, nonneuritic plaques (sometimes referred to as burned-out plaques) are thought to represent an end stage of plaque evolution (1) (for schematic representation of plaque progression, please see Fig. 1A).

Keywords

Down Syndrome Microglial Activation Temporal Lobe Epilepsy Inflammatory Pathway Dense Core 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rozemuller, J. M., Eikelenboom, P., Stam, F. C., Beyreuther, K., and Masters, C. L. (1989) A4 protein in Alzheimer’s disease: primary and secondary cellular events in extracellular amyloid deposition, J. Neuropathol. Exp. Neurol. 48, 674–691.PubMedCrossRefGoogle Scholar
  2. 2.
    Griffin, W. S. T., Stanley, L. C., Ling, C., White, L., Macleod, V., Perrot, L. J., White, C. L., III, and Araoz, C. (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease, Proc. Nall. Acad. Sci. USA. 86, 7611–7615.CrossRefGoogle Scholar
  3. 3.
    Rozemuller, J. M., Stam, F. C., and Eikelenboom, P. (1990) Acute phase proteins are present in amorphous plaques in the cerebral but not cerebellar cortex of patients with Alzheimer’s disease, Neurosci. Lett. 119, 75–78.PubMedCrossRefGoogle Scholar
  4. 4.
    Griffin, W. S. T., Sheng, J. G., Roberts, G. W., and Mrak, R. E. (1995) Interleukin-1 expression in different plaque types in Alzheimer’s disease, J. Neuropathol. Exp. Neurol. 54, 276–281.PubMedCrossRefGoogle Scholar
  5. 5.
    Mrak, R. E., Sheng, J. G., and Griffin, W. S. T. (1996) Correlation of astrocytic S100(3 expression with dystrophic neurites in amyloid plaques of Alzheimer’s disease, J. Neuropathol. Exp. Neurol. 55, 273–279.PubMedCrossRefGoogle Scholar
  6. 6.
    Righi, M., Mori, L., De Libero, G., Sironi, M., Biondi, A., Mantovani, A., Donini, S. D., and Ricciardi-Castagonoli, R. (1989) Monokine production by microglial cell clones, Eur. J. Immunol. 19, 1443–1448.PubMedCrossRefGoogle Scholar
  7. 7.
    Brenneman, D. E., Schultzberg, M., Bartfai, T., and Gozes, I. (1992) Cytokine regulation of neuronal survival, J. Neurochem. 58, 454–460.PubMedCrossRefGoogle Scholar
  8. 8.
    Giulian, D. and Lachman, L. B. (1985) Interleukin-1 stimulation of astroglial proliferation after brain injury, Science 228, 497–499.PubMedCrossRefGoogle Scholar
  9. 9.
    Thomas, W. E. (1992) Brain macrophages: evaluation of microglia and their functions, Brain Res. Rev. 17, 61–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Goldgaber, D., Harris, H. W., Hla, T., Maciag, T., Donnelly, R. G., Jacobsen, J. S., Vitek, M. R, and Gajdusek, D. C. (1989) Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells, Proc. Natl. Acad. Sci. USA 86, 7606–7610.PubMedCrossRefGoogle Scholar
  11. 11.
    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, Brain Res. Mol. Brain Res. 16, 128–134.PubMedCrossRefGoogle Scholar
  12. 12.
    Donnelly, R. J., Freidhoff, A. J., Beer, B., Blume, A. J., and Vitek, M. P. (1990) Interleukin-1 stimulates the beta-amyloid precursor protein promoter, Cell. Mol. Neurobiol. 10, 485–495.PubMedCrossRefGoogle Scholar
  13. 13.
    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/A4 amyloid protein precursor, Proc. Natl. Acad. Sci. USA. 89, 10075–10078.PubMedCrossRefGoogle Scholar
  14. 14.
    Ganter, S., Northoff, H., Mannel, D., and Gebicke-Harter, R. J. (1992) Growth control of cultured microglia, J. Neurosci. Res. 33, 218–230.PubMedCrossRefGoogle Scholar
  15. 15.
    Sebire, G., Emilie, D., Wallon, C., Hery, C., Devergne, O., Delfraissy, J. F., Galanaud, P., and Tardieu, M. (1993) In vitro production of IL-6, IL-1 beta, and tumor necrosis factor-alpha by human embryonic microglial and neural cells, J. Immunol. 150, 1517–1523.PubMedGoogle Scholar
  16. 16.
    Lee, S. C., Liu, W., Dickson, D. W., Brosnan, C. F., and Berman, J. W. (1993) Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta, J Immunol. 150, 2659–2667.PubMedGoogle Scholar
  17. 17.
    Giulian, D., Woodward, J.,Young, D. G., Krebs, J. F., and Lachman, L. B. (1988) Interleukin1 injected into mammalian brain stimulates astrogliosis and neovascularization, J. Neurosci. 8, 2485–2490.Google Scholar
  18. 18.
    Berkenbosch, F., Robakin, N., and Blum, M. (1991) Interleukin-1 in the central nervous system: a role in the acute phase response and in brain injury, brain development and the pathogenesis of Alzheimer’s disease, in Peripheral Signaling of the Brain. Role in Neural-Immune Interactions, Learning and Memory ( Frederickson, R. C. A., McGaugh, J. L., and Felten, D. L., eds.), Hogrefe and Huber, Toronto, pp. 131–145.Google Scholar
  19. 19.
    Sheng, J. G., Ito, K., Skinner, R. D., Mrak, R. E., Rovnaghi, C. R., Van Eldik, L. J., and Griffin, W. S. T. (1996) In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis, Neurobiol. Aging in press.Google Scholar
  20. 20.
    Frohman, E. M., van den Noort, S., and Gupta, S. (1989) Astrocytes and intracerebral immune responses, J Clin. Immunol. 9, 1–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Perlmutter, D. H., Dinarello, C. A., Punsal, P. I., and Colten, H. R. (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression, J Clin. Invest. 78, 1349–1354.PubMedCrossRefGoogle Scholar
  22. 22.
    Das, S., Geller, L., Niethammer, M., and Potter, H. (1994) Expression of the Alzheimer amyloid-promoting factors al-antichymotrypsin and apolipoprotein E is induced in astrocytes by IL-1, Neurobiol. Aging 15, S17.Google Scholar
  23. 23.
    Rus, H. G., Kim, L. M., Niculescu, F. I., and Shin, M. L. (1992) Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus, J. Immunol. 148, 928–933.PubMedGoogle Scholar
  24. 24.
    Marshak, D. R., Pesce, S. A., Stanley, L. C., and Griffin, W. S. T. (1992) Increased S100ß neurotrophic activity in Alzheimer disease temporal lobe, Neurobiol. Aging 13, 1–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Sheng, J. G., Mrak, R. E., and Griffin, W. S. T. (1994) S 10013 protein expression in Alzheimer’s disease: potential role in the pathogenesis of neuritic plaques, J. Neurosci. Res. 39, 398–404.PubMedCrossRefGoogle Scholar
  26. 26.
    Marshak, D. R. (1990) S100113 as a neurotrophic factor, Prog. Brain Res. 86, 169–181.PubMedCrossRefGoogle Scholar
  27. 27.
    Barger, S. W. and Van Eldik, L. J. (1992) S10013 stimulates calcium fluxes in glial and neuronal cells, J. Biol. Chem. 267, 9689–9694.PubMedGoogle Scholar
  28. 28.
    Selinfreund, R. H., Barger, S. W., Pledger, W. J., and Van Eldik, L. J. (1991) Neurotrophic protein S100ß stimulates glial cell proliferation, Proc. Natl. Acad. Sci. USA. 88, 3554–3558.PubMedCrossRefGoogle Scholar
  29. 29.
    Kligman, D. and Marshak, D. R. (1985) Purification and characterization of a neurite extension factor from bovine brain, Proc. Natl. Acad. Sci. USA 82, 7136–7139.PubMedCrossRefGoogle Scholar
  30. 30.
    Rogers, J., Cooper, N. R., Webster, S., Schultz, J., McGeer, P. L., Styren, S. D., Civin, W. H., Brachova, L., Bradt, B., and Ward, P. (1992) Complement activation by beta-amyloid in Alzheimer disease, Proc. Natl. Acad. Sci. USA. 89, 10016–10020.PubMedCrossRefGoogle Scholar
  31. 31.
    Wisniewski, K. E., Wisniewski, H. M., and Wen, G. Y. (1985) Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome, Ann. Neurol. 17, 278–282.PubMedCrossRefGoogle Scholar
  32. 32.
    Baggott, P. J., Sheng, J. G., Cork, L., Del Biggio, M. R., Brumback, R., Roberts, G. W., Mrak, R. E., and Griffin, W. S. T. (1993) Expression of Alzheimer’s disease (AD)-related proteins during development in Down’s syndrome (DS), Soc. Neurosci. Abstract 19 (part 1), 182.Google Scholar
  33. 33.
    Allore, R., O’Hanlon, D., Price, R., Neilson, K., Willard, H. F., Cox, D. R., Marks, A., and Dunn, R. J. (1988) Gene encoding the ß subunit of 5100 protein is on chromosome 21: implications for Down syndrome, Science 239, 1311–1313.PubMedCrossRefGoogle Scholar
  34. 34.
    Tanzi, R. E., Gusella, J. F., Watkins, P. C., Bruns, G. A., St. George-Hyslop, P., Van Keuren, M. L., Patterson, D., Pagan, S., Kurnit, D. M., and Neve, R. L. (1987) Amyloid 13 protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus, Science 235, 880–884.PubMedCrossRefGoogle Scholar
  35. 35.
    Goldgaber, D., Lerman, M. L., McBride, W. O., Saffiotti, U., and Gajdusek, D. C. (1987) Isolation, characterization, and chromosomal localization of human brain cDNA clones coding for the precursor of the amyloid of brain in Alzheimer’s disease, Down’s syndrome and aging, J. Neural Transm. 24 (Suppl.), 23–28.Google Scholar
  36. 36.
    Boultwood, J., Breckon, G., Birch, D., and Cox, R. (1989) Chromosomal localization of murine interleukin-1 alpha and beta genes, Genomics 5, 481–485.PubMedCrossRefGoogle Scholar
  37. 37.
    Gautrin, D. and Gauthier, S. (1989) Alzheimer’s disease: environmental factors and etiologic hypotheses, Can. J Neurol. Sci. 16, 375–387.PubMedGoogle Scholar
  38. 38.
    Graves, A. B., White, E., Koepsell, T. D., Reifler, B. V., van Belle, G., Larson, E. B., and Raskind, M. (1990) The association between head trauma and Alzheimer’s disease, Am. J. Epidemiol. 131, 491–501.PubMedGoogle Scholar
  39. 39.
    Mayeux, R., Ottman, R., Tang, M. X., Noboa-Bauza, L., Marder, K., Gurland, B., and Stern, Y. (1993) Genetic susceptibility and head injury as risk factors for Alzheimer’s disease among community-dwelling elderly persons and their first-degree relatives, Ann. Neurol. 33, 494–501.PubMedCrossRefGoogle Scholar
  40. 40.
    Gentleman, S. M., Nash, M. J., Sweeting, C. J., Graham, D. I., and Roberts, G. W. (1993) 13-amyloid precursor protein (I3-APP) as a marker for axonal injury after head injury, Neurosci. Lett. 160, 139–144.Google Scholar
  41. 41.
    Griffin, W. S. T., Sheng, J. G., Gentleman, S. M., Graham, D. I., Mrak, R. E., and Roberts, G. W. (1995) Microglial interleukin-la expression in human head injury: correlations with neuronal and neuritic (3-amyloid precursor protein expression, Neurosci. Lett. 176, 133–136.CrossRefGoogle Scholar
  42. 42.
    Sheffield, L. G., Purcell, J. A., and Berman, N. E. J. (1995) Microglial activation in monkeys increases with age, Soc. Neurosci. Abstract 21 (part 1), 470.Google Scholar
  43. 43.
    Sheng, J. G., Mrak, R. E., Rovnaghi, C. R., Kozlowska, E., Van Eldik, L. J., and Griffin, W. S. T. (1996) Human brain S10013 and S1003 mRNA expression increases with age: pathogenic implications for Alzheimer’s disease, Neurobiol. Aging 17, 359–363.PubMedCrossRefGoogle Scholar
  44. 44.
    Kato, K., Suzuki, F., Morishita, R., Asano, T., and Sato, T. (1990) Selective increase in S-10013 protein by aging in rat cerebral cortex, J Neurochem. 54, 1269–1274.PubMedCrossRefGoogle Scholar
  45. 45.
    Mackenzie, I. R. A. and Miller, L. A. (1994) Senile plaques in temporal lobe epilepsy, Acta Neuropathol. 87, 504–510.PubMedCrossRefGoogle Scholar
  46. 46.
    Sheng, J. G., Boop, F. A., Mrak, R. E., and Griffin, W. S. T. (1994) Increased neuronal betaamyloid precursor protein expression in human temporal lobe epilepsy: association with interleukin-1 alpha immunoreactivity, J. Neurochem. 63, 1872–1879.PubMedCrossRefGoogle Scholar
  47. 47.
    Griffin, W. S. T., Yeralan, O., Sheng, J. G., Boop, F. A., Mrak, R. E., Rovnaghi, C. R., Burnett, B. A., Feoktistova, A., and Van Eldik, L. J. (1995) Overexpression of the neurotrophic cytokine S 10013 in human temporal lobe epilepsy, J Neurochem. 65, 228–233.PubMedCrossRefGoogle Scholar
  48. 48.
    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 non-steroidal anti-inflammatory and histamine H2 blocking drugs, Neurobiol. Aging 16, 523–530.PubMedCrossRefGoogle Scholar
  49. 49.
    Pasternack, J. M., Abraham, C. R., Van Dijcke, B. J., Potter, H., and Younkin, S. G. (1989) Astrocytes in Alzheimer’s disease grey matter express alpha l-antichymotrypsin mRNA, Am. J Pathol. 135, 827–834.PubMedGoogle Scholar
  50. 50.
    Levi-Strauss, M. and Mallat, M. (1987) Primary cultures of murine astrocytes produce C3 and factor B, two components of the alternative pathway of complement activation, J. Immunol. 139, 2361–2366.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • W. Sue T. Griffin
  • Jin G. Sheng
  • Robert E. Mrak

There are no affiliations available

Personalised recommendations