Acta Neuropathologica

, Volume 81, Issue 2, pp 105–110 | Cite as

Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia

  • I. Grundke-Iqbal
  • J. Fleming
  • Y. -C. Tung
  • H. Lassmann
  • K. Iqbal
  • J. G. Joshi
Regular Papers

Summary

A strong immunoreactivity for ferritin was observed in the neuritic (senile) plaques in Alzheimer's disease hippocampus. The ferritin accumulation was almost exclusively associated with the microglia, which appeared to have proliferated greatly. These cells were also positive for HLA-DR, a putative marker for reactive microglia. In contrast, in the diffuse plaques, which were without neuritic pathology, the ferritin-stained microglia appeared to be normal. Microglia were seen frequently in contact with neurons undergoing neurofibrillary changes but only the tangles in the extracellular space were ferritin positive. No ferritin was detected, by Western blots, in paired helical filaments isolated from Alzheimer's disease brain, suggesting that ferritin was most likely weakly associated with and was not a constituent of these fibrils. No correlation between increased ferritin/microglia activity and blood-brain barrier leakage was detected. Ferritin, an iron-storage protein, might have a role in the formation of amyloid through the action of free radicals generated during the release of iron from the ferritin molecule. Alternatively, the ferritin/microglia system might be secondarily involved in the removal and processing of the amyloid.

Key words

Microglia Amyloid Ferritin Paired helical filaments Alzheimer's disease 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Alafuzoff I, Adolfsson R, Grundke-Iqbal I, Winblad B (1987) Blood-brain barrier in Alzheimer dementia and in nondemented elderly: an immunocytochemical study. Acta Neuropathol (Berl) 73:160–166Google Scholar
  2. 2.
    Andersson KB, Sletten K, Brentzen HB, Dale I, Brandtzaeg P, Jellum E, Fagerhol MK (1988) The leucocyte LI protein: identity with the cystic fibrosis antigen and the calcium-binding MRP-8 and MRP-14 macrophage components. Scand J Immunol 28:241–245Google Scholar
  3. 3.
    Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477:90–99Google Scholar
  4. 4.
    Eikelenboom P, Stam FC (1982) Immunoglobulins and complement factors in senile plaques. An immunoperoxidase study. Acta Neuropathol (Berl) 57:239–242Google Scholar
  5. 5.
    Esiri MM, McGee JD (1986) Monoclonal antibody to macrophages (EMB/II) labels macrophages and microglia in human brain. J Clin Pathol 39:615–621Google Scholar
  6. 6.
    Fleming J, Joshi JG (1987) Ferritin: isolation of aluminumferritin complex from brain. Proc Natl Acad Sci USA 84:7866–7870Google Scholar
  7. 7.
    Frei K, Siepl CH, Groscurth P, Bodmer S, Schwerdel C, Fontana A (1987) Antigen presentation and tumor toxicity by interferon-gamma-treated microglial cells. Eur J Immunol 17:1271–1278Google Scholar
  8. 8.
    Gerber MR, Connor JR (1989) Do oligodendrocytes mediate iron regulation in the human brain? Neurology 26:95–98Google Scholar
  9. 9.
    Glenner GG, Wong CW (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890Google Scholar
  10. 10.
    Grundke-Iqbal I, Vorbrodt AW, Iqbal K, Tung Y-C, Wang GP, Wisniewski HM (1988) Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments. Mol Brain Res 4:43–52Google Scholar
  11. 11.
    Grundke-Iqbal I, Iqbal K, George L, Tung Y-C, Kim KS, Wisniewski HM (1989) Amyloid protein and neurofibrillary tangles coexist in the same neuron in Alzheimer disease. Proc Natl Acad Sci USA 86:2853–2857Google Scholar
  12. 12.
    Iqbal K, Zaidi T, Thompson CH, Merz PA, Wisniewski HM (1984) Alzheimer paired helical filaments: bulk isolation, solubility and protein composition. Acta Neuropathol (Berl) 62:167–177Google Scholar
  13. 13.
    Joshi JG, Clauberg M (1988) Ferritin: an iron storage protein with diverse functions. BioFactors 1:207–212Google Scholar
  14. 14.
    Kaneko Y, Kitamoto T, Tateishi J, Yamaguchi K (1989) Ferritin immunochemistry as a marker for microglia. Acta Neuropathol 79:129–136Google Scholar
  15. 15.
    Masters CL, Simms G, Weinman NA, Multhaup G, Macdonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer's disease and Down's syndrome. Proc Natl Acad Sci USA 82:4245–4249Google Scholar
  16. 16.
    McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology 38:1285–1291Google Scholar
  17. 17.
    Merz PA, Wisniewski HM, Bobin SA, Masters CL, Iqbal K (1983) Ultrastructural morphology of amyloid fibrils from neuritic and amyloid plaques. Acta Neuropathol (Berl) 60:113–124Google Scholar
  18. 18.
    Perl DP, Brody AR (1980) Alzheimer's disease. X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208:297–299Google Scholar
  19. 19.
    Perl DP, Gajdusek DC, Garruto RM, Yanagihara RT, Gibbs CJ Jr (1982) Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Science 217:1053–1055Google Scholar
  20. 20.
    Probst A, Brunnschweiler H, Lautenschlager V, Ulrich J (1987) A special type of senile plaque, possibly an initial state. Acta Neuropathol (Berl) 74:133–141Google Scholar
  21. 21.
    Rozemuller JM, Eikelenboom P, Pals ST, Stam FC (1989) Microglial cells around amyloid plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family. Neurosci Lett 101:288–292Google Scholar
  22. 22.
    Rozemuller JM, Eikelenboom P, Stam FC, Beyreuther K, Masters CL (1989) A4 protein in Alzheimer's disease: primary and secondary cellular events in extracellular amyloid deposition. J Neuropathol Exp Neurol 48:674–691Google Scholar
  23. 23.
    Sternberger LA, Hardy PH Jr, Cuculius JJ, Meyer HG (1970) The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-anti-peroxidase) and its use in identification of spirochetes. J Histochem Cytochem 18:315–333Google Scholar
  24. 24.
    Tagliavini F, Giaccone G, Frangione B, Bugiani O (1988) Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals. Neurosci Lett 93:191–196Google Scholar
  25. 25.
    Tago H, McGeer PL, Bruce G, Hersch LB (1987) Distribution of choline acetyltransferase containing neurons of the hypothalamus. Brain Res 415:49–62Google Scholar
  26. 26.
    Wang GP, Grundke-Iqbal I, Kascsak RJ, Iqbal K, Wisniewski HM (1984) Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s). Acta Neuropathol (Berl) 62:268–275Google Scholar
  27. 27.
    Wegiel J, Wisniewski HM (1990) Ultrastructural study of diffuse amyloid deposits (abstract). J Neuropathol Exp Neurol 49:268Google Scholar
  28. 28.
    Wisniewski HM, Sinatra RS, Iqbal K, Grundke-Iqbal I (1981) Neurofibrillary and synaptic pathology in the aged brain. In: Johnson JE Jr (ed) Aging and cell structure, vol 1 Plenum, New York, pp 105–142Google Scholar
  29. 29.
    Wisniewski HM, Wegiel J, Wang KC, Kujawa M, Lach B (1989) Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci 16:535–542Google Scholar
  30. 30.
    Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Harigaya Y (1988) Diffuse type of senile plaques in the brains of Alzheimer-type dementia. Acta Neuropathol 77:113–119Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • I. Grundke-Iqbal
    • 1
  • J. Fleming
    • 2
  • Y. -C. Tung
    • 1
  • H. Lassmann
    • 3
    • 4
  • K. Iqbal
    • 1
  • J. G. Joshi
    • 2
  1. 1.New York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  2. 2.Department of BiochemistryUniversity of TennesseeKnoxvilleUSA
  3. 3.Institute for Brain ResearchAustrian Academy of SciencesViennaAustria
  4. 4.Neurological InstituteUniversity of ViennaViennaAustria

Personalised recommendations