The Histochemical Journal

, Volume 21, Issue 11, pp 659–662 | Cite as

Immunohistochemical evidence for reorganization of tau in the plaques and tangles in Alzheimer's dissease

  • John G. Wood
  • Philip Zinsmeister
Papers

Summary

Cytochemical and biochemical techniques have been used to assess the relationship of epitopes on the microtubuleassociated protein, tau, to the cytoskeletal pathology of Alzheimer's disease. The main probes were Tau-1 and Alz-50, two monoclonal antibodies which recognize tau and a potentially related 68kDa protein. Sequential treatment of tissue slices with combinations of the antibodies showed that each blocked the binding of the other to neurofibrillary tangles and neuritic plaques but not to normal axons. Western blot analysis of tau proteins isolated from Alzheimer's disease brains did not reveal such blocking patterns. The issue of steric hindrance affecting antibody binding in tissue sections was addressed by using Alz-50 in combination with Tau-2, another monoclonal antibody recognizing tau on blots and in Alzheimer's disease pathology. Neither antibody blocked the binding of the other to neurofibrillary tangles and neuritic plaques. These data suggest that the Alz-50 and Tau-1 epitopes are selectively organized in the tangles and plaques to be in close proximity which supports the hypothesis that in Alzheimer's disease pathology, tau is modified.

Keywords

Steric Hindrance Antibody Binding Neurofibrillary Tangle Disease Brain Sequential Treatment 

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References

  1. Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M. &Binder, L. I. (1986) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology.Proc. Natl. Acad. Sci. USA 83, 4913.Google Scholar
  2. Kosik, K. S., Joachim, C. L. &Selkoe, D. J. (1986) Microtubule-associated protein tau is a major antigenic component of paired helical filaments in Alzheimer disease.Proc. Natl. Acad. Sci. USA 83, 4040.Google Scholar
  3. Ksiezak-Reding, H., Binder, L. I. &Yen, S.-H. (1988a) Immunochemical and biochemical characterization of tau proteins in normal and Alzheimer's disease brains with Alz 50 and Tau-1.J. Biol. Chem. 263, 7948.Google Scholar
  4. Ksiezak-Reding, H., Davies, P. &Yen, S.-H. (1988b) Alz 50, a monoclonal antibody to Alzheimer's disease antigen cross-reacts with tau proteins from bovine and normal human brain.J. Biol. Chem. 263, 7943.Google Scholar
  5. Papasozomenos, S. C. &Binder, L. I. (1987) Phosphorylation determines two distinct species of tau in the central nervous system.Cell Motil. Cytoskel. 8, 210.Google Scholar
  6. Pollock, N. J. &Wood, J. G. (1988) Differential sensitivity of the microtubule-associated protein, tau, in Alzheimer's disease tissue to formalin fixation.J. Histochem. Cytochem. 36, 1117.Google Scholar
  7. Pollock, N. J., Binder, L. I., Mirra, S. S. & Wood, J. G. (1988) Alzheimer's disease: a model for study of cytoskeletal segregation as a determinant of neuronal form and function. InIntrinsic Determinants of Neuronal Form. p. 569. Alan R. Liss.Google Scholar
  8. Pollock, N. J., Mirra, S. S., Binder, L. I., Hansen, L. A. &Wood, J. G. (1986) Filamentous aggregates in Pick's disease, progressive supranuclear palsy and Alzheimer's disease share antigenic determinants with microtubule-associated protein, tau.Lancet 22, 1211.Google Scholar
  9. Wood, J. G., Mirra, S. S., Pollock, N. J. &Binder, L. I. (1986) Neurofibrillary tangles of Alzheimer's disease share antigenic determinants with the axonal microtuble-associated protein, tau.Proc. Natl. Acad. Sci. USA 83, 4040.Google Scholar

Copyright information

© Chapman and Hall Ltd. 1989

Authors and Affiliations

  • John G. Wood
    • 1
  • Philip Zinsmeister
    • 2
  1. 1.Department of Anatomy and Cell BiologyEmory University School of MedicineAtlantaUSA
  2. 2.Department of BiologyOglethorpe UniversityAtlantaUSA

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