Skip to main content
SpringerLink
Log in

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

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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) 73:160–166

    Google Scholar 

  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 28:241–245

    Google Scholar 

  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 477:90–99

    Google Scholar 

  4. Eikelenboom P, Stam FC (1982) Immunoglobulins and complement factors in senile plaques. An immunoperoxidase study. Acta Neuropathol (Berl) 57:239–242

    Google Scholar 

  5. Esiri MM, McGee JD (1986) Monoclonal antibody to macrophages (EMB/II) labels macrophages and microglia in human brain. J Clin Pathol 39:615–621

    Google Scholar 

  6. Fleming J, Joshi JG (1987) Ferritin: isolation of aluminumferritin complex from brain. Proc Natl Acad Sci USA 84:7866–7870

    Google Scholar 

  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 17:1271–1278

    Google Scholar 

  8. Gerber MR, Connor JR (1989) Do oligodendrocytes mediate iron regulation in the human brain? Neurology 26:95–98

    Google Scholar 

  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 120:885–890

    Google Scholar 

  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 4:43–52

    Google Scholar 

  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 86:2853–2857

    Google Scholar 

  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) 62:167–177

    Google Scholar 

  13. Joshi JG, Clauberg M (1988) Ferritin: an iron storage protein with diverse functions. BioFactors 1:207–212

    Google Scholar 

  14. Kaneko Y, Kitamoto T, Tateishi J, Yamaguchi K (1989) Ferritin immunochemistry as a marker for microglia. Acta Neuropathol 79:129–136

    Google Scholar 

  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 82:4245–4249

    Google Scholar 

  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 38:1285–1291

    Google Scholar 

  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) 60:113–124

    Google Scholar 

  18. Perl DP, Brody AR (1980) Alzheimer's disease. X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 208:297–299

    Google Scholar 

  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 217:1053–1055

    Google Scholar 

  20. Probst A, Brunnschweiler H, Lautenschlager V, Ulrich J (1987) A special type of senile plaque, possibly an initial state. Acta Neuropathol (Berl) 74:133–141

    Google Scholar 

  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 101:288–292

    Google Scholar 

  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 48:674–691

    Google Scholar 

  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 18:315–333

    Google Scholar 

  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 93:191–196

    Google Scholar 

  25. Tago H, McGeer PL, Bruce G, Hersch LB (1987) Distribution of choline acetyltransferase containing neurons of the hypothalamus. Brain Res 415:49–62

    Google Scholar 

  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) 62:268–275

    Google Scholar 

  27. Wegiel J, Wisniewski HM (1990) Ultrastructural study of diffuse amyloid deposits (abstract). J Neuropathol Exp Neurol 49:268

    Google Scholar 

  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 105–142

    Google Scholar 

  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 16:535–542

    Google Scholar 

  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 77:113–119

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, 10314, Staten Island, NY, USA

    I. Grundke-Iqbal, Y. -C. Tung & K. Iqbal

  2. Department of Biochemistry, University of Tennessee, 37996-0840, Knoxville, TN, USA

    J. Fleming & J. G. Joshi

  3. Institute for Brain Research, Austrian Academy of Sciences, Vienna, Austria

    H. Lassmann

  4. Neurological Institute, University of Vienna, Vienna, Austria

    H. Lassmann

Authors
  1. I. Grundke-Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Fleming
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. -C. Tung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Lassmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Iqbal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. G. Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by the New York State Office of Mental Retardation and Developmental Disabilities and National Institutes of Health grants NS18105, AG05892 and AG04220. H. L. was funded by a grant from the Ministry for Science and Research, Austria, J. G. J. and J. F. were funded by the Council for Tobacco Research. Parts of this paper have been reported at the 9th International Conference on Proteins of Iron Transport and Storage, Brisbane, Australia, June 1989 and at the 2nd International Conference on Aluminium and Health, Orlando, Fla, USA, December 1989

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grundke-Iqbal, I., Fleming, J., Tung, Y.C. et al. Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia. Acta Neuropathol 81, 105–110 (1990). https://doi.org/10.1007/BF00334497

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00334497

Key words

Search

Navigation