Acta Neuropathologica

, Volume 90, Issue 1, pp 51–56 | Cite as

White matter amyloid in Alzheimer's disease brain

  • Toshiki Uchihara
  • Hiromi Kondo
  • Haruhiko Akiyama
  • Kenji Ikeda
Regular Paper

Abstract

Amyloid β-protein (Aβ) deposits in the white matter were investigated by the double immunohistochemical staining for Aβ and neuritic, glial or vascular components. Reactive astroglia and neurite abnormality were absent around Aβ deposits in the white matter (w-Aβ) even those with a core. The association of w-Aβ with blood vessels was not consistent. Aggregates of activated microglia were found to be the sole but a consistent accompaniment of Aβ deposits even in the absence of other components such as neuron, synapse, neurite abnormality and reactive astroglia, as observed in the white matter. This suggests that the aggregates of activated microglia most likely represent one of the factors promoting the process of Aβ deposition.

Key words

β-Protein White matter Laser scanning microscopy Microglia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Akiyama H, Ikeda K, Kondo H, McGeer PL (1992) Thrombin accumulation in brains of patients with Alzheimer's disease. Neurosci Lett 146:152–154Google Scholar
  2. 2.
    Barcikowska M, Wisniewski HM, Bancher C, Grundke-Iqbal I (1989) About the presence of paired helical filaments in dystrophic neurites participating in the plaque formation. Acta Neuropathol 78:225–231Google Scholar
  3. 3.
    Behrouz N, Defossez A, Delacourte A Hublau P, Mazzuca M (1989) Alzheimer's disease: glycolytic pretreatment dramatically enhances immunolabeling of senile plaques and cerebrovascular amyloid substance. Lab Invest 61:576–583Google Scholar
  4. 4.
    Behrouz N, Defossez A, Delacourte A, Mazzuca M (1990) Cortical β-amyloid. Nature 344:497Google Scholar
  5. 5.
    Behrouz N, Defossez A, Delacourte A, Mazzuca M (1991) The immunohistochemical evidence of amyloid diffuse deposits as a pathological hallmark in Alzheimer's disease. J Gerontol 46:B209–212Google Scholar
  6. 6.
    Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, Glabe C (1992) Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs. J Biol Chem 267:546–554Google Scholar
  7. 7.
    Cras P, Kawai M, Siedlak S, Mulvihill P, Lowery D, Gonzalez-De Whitt P, Greenberg B, Perry G (1990) Neuronal and microglial involvement in beta-amyloid protein deposition in Alzheimer's disease. Am J Pathol 137:241–246Google Scholar
  8. 8.
    Davis JB, McMurray HF, Schubert D (1992) The amyloid betaprotein of Alzheimer's disease is chemotactic for mononuclear phagocytes. Biochem Biophys Res Commun 189:1096–1100Google Scholar
  9. 9.
    Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen SC (1988) Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am J Pathol 132:86–101Google Scholar
  10. 10.
    Frackowiak J, Wisniewski HM, Wegiel J, Merz GS, Iqbal K, Wang C (1992) Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. Acta Neuropathol 84:225–233Google Scholar
  11. 11.
    Fraser PE, Nguyen JT, Chin DT, Kirschner DA (1992) Effects of sulfate ions on Alzheimer beta/A4 peptide assembilies: implications for amyloid fibril-proteoglycan interactions. J Neurochem 59:1531–1540Google Scholar
  12. 12.
    Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski BL, Lieberburg I, Koo EH, Schenk D, Teplow DB, Selkoe DJ (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359: 322–325Google Scholar
  13. 13.
    Haga S, Akai K, Ishii T (1989) Demonstration of microglial cells in and around senile (neuritic) plaques in Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol 77:569–575Google Scholar
  14. 14.
    Itagaki S, McGeer PL, Akiyama H, Zhu S, Selkoe D (1989) Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J Neuroimmunol 24:173–182Google Scholar
  15. 15.
    Jenkinson ML, Bliss MR, Brain AT, Scott DL (1989) Rheumatoid arthritis and senile dementia of the Alzheimer's type. Br J Rheumatol 26:86–88Google Scholar
  16. 16.
    Kawai M, Kalaria RN, Harik SI, Perry G (1990) The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease. Am J Pathol 137:1435–1446Google Scholar
  17. 17.
    McGeer PL, Rogers J, (1992) Anti-inflammatory agents as a therapeutic approach to Alzheimer's disease. Neurology 42:447–449Google Scholar
  18. 18.
    McGeer PL, McGeer E, Rogers J, Sibley J (1990) Anti-inflammatory drugs and Alzheimer disease. Lancet 335:1037Google Scholar
  19. 19.
    Miyazono M, Iwaki T, Kitamoto T, Kaneko Y, Doh-ura K, Tateishi J (1991) A comparative immunohistochemical study of Kuru and senile plaques with a special reference to glial reactions at various stages of amyloid plaque formation. Am J Pathol 139:589–598Google Scholar
  20. 20.
    Perlmutter LS, Barron E, Chui HC, (1990) Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. Neurosci Lett 119:32–36Google Scholar
  21. 21.
    Probst A, Brunnschweiler H, Lautenschlager C, Ulrich J (1987) A special type of senile plaque, possibly an initial stage. Acta Neuropathol (Berl). 74:133–141Google Scholar
  22. 22.
    Rogers J, Cooper NR, Webster S, Schultz J, McGeer PL, Styren SD, Civin WH, Brachova L, Bradt B, Ward P (1992) Complement activation by beta-amyloid in Alzheimer disease. Proc Natl Acad Sci USA 89:10016–10020Google Scholar
  23. 23.
    Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, Kogan F (1993) Clinical trial of indomethachin in Alzheimer's disease. Neurology 43:1609–1611Google Scholar
  24. 24.
    Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, McCormack R, Wolfert R, Selkoe D, Lieberburg I, Schenk D (1992) Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluid. Nature 359:325–327Google Scholar
  25. 25.
    Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai X-D, McKay DM, Tintner R, Frangione B, Younkin S (1992) Production of the alzheimer amyloid beta protein by normal proteolytic processing. Science 258:126–129Google Scholar
  26. 26.
    Styren SD, Civin WH, Rogers J (1990) Molecular, cellular, and pathologic characterization of HLA-DR immunoreactivity in normal elderly and Alzheimer's disease brain. Exp Neurol 110:93–104Google Scholar
  27. 27.
    Ulrich J (1985) Alzheimer changes in nondemented patients younger than sixty-five: possible early stages of Alzheimer's disease and senile dementia of Alzheimer type. Ann Neurol 17: 273–277Google Scholar
  28. 28.
    Wegiel J, Wisniewski HM (1990) The complex of microglial cells and amyloid star in three-dimensional reconstruction. Acta Neuropathol 81:116–124Google Scholar
  29. 29.
    Wisniewski HM, Wegiel J (1991) Spatial relationships between astrocytes and classical plaque components. Neurobiol Aging 12:593–600Google Scholar
  30. 30.
    Wisniewski HM, Bancher C, Barcikowska M, Wen GY, Cirrie J (1989) Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease. Acta Neuropathol 78:337–347Google Scholar
  31. 31.
    Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Harigaya Y (1988) Diffuse type of seniles plaques in the brains of Alzheimer-type dementia. Acta Neuropathol 77:113–119Google Scholar
  32. 32.
    Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Ihara Y (1988) A variety of cerebral amyloid deposits in the brains of the Alzheimer-type dementia demonstrated by beta protein immunostaining. Acta Neuropathol 76:541–549Google Scholar
  33. 33.
    Yamaguchi H, Nakazato Y, Hirai S, Shoji M, Harigaya Y (1989) Electron micrograph of diffuse plaques: initial stage of senile plaque formation in the Alzheimer brain. Am J Pathol 135:593–597Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Toshiki Uchihara
    • 1
    • 2
    • 3
  • Hiromi Kondo
    • 2
  • Haruhiko Akiyama
    • 2
  • Kenji Ikeda
    • 2
  1. 1.Department of Neurology, Faculty of MedicineTokyo Medical and Dental UniversityTokyoJapan
  2. 2.Department of NeuropathologyTokyo Institute of PsychiatryTokyoJapan
  3. 3.Laboratories R. Escourolle, Service de NeuropathologieGroupe Hospitalier La Petié-La SalpêtrièreParis, CEDEXFrance

Personalised recommendations