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Correlation between microscopical changes and Tau 64 and 69 biochemical detection in senile dementia of the Alzheimer type

Tau 64 and 69 are reliable markers of the neurofibrillary degeneration

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Summary

We have recently reported that the immunoblot detection of two abnormally phosphorylated tau proteins, named Tau 64 and 69, in homogenates of cortical areas from patients with Alzheimer's disease (AD) was systematically associated with the presence of neurofibrillary tangles (NFT) and senile plaques (SP) in these areas. A blind study was performed to confirm that these proteins had a reliable diagnostic value and to study more precisely the correlation between Tau 64 and 69 and the presence of the characteristic lesions of AD. The density of NFT and of SP was evaluated on histological sections of gyrus supramarginalis from 17 patients with graded intellectual status. Immunodetection of Tau 64 and 69 was semiquantitatively evaluated by densitometry (reflectance mode) on immunoblots of homogenates of the same area on the contralateral hemisphere. The statistical analysis of results showed that Tau 64 and 69 were more strongly correlated with NFT than with SP. Moreover, semiquantitative evaluation of Tau 64 and 69 was correlated with the intellectual status (BTS score). Therefore, these pathological forms of tau proteins are reliable markers of the presence of NFT and SP in the neocortex and may be used as a diagnostic tool.

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References

  1. Blessed G, Tomlinson BE, Roth M (1968) The Association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114:797–811

    Google Scholar 

  2. Brion JP, Passareiro H, Nunez J, Flament-Durand J (1985) Mise en évidence immunologique de la protéine tau au niveau des lésions de dégénérescence neurofibrillaire de la maladie d'Alzheimer. Arch Biol 95:229–235

    Google Scholar 

  3. Defossez A, Beauvillain JC, Delacourte A, Mazzuca M (1988) Alzheimer's disease: a new evidence for common epitopes between microtubule associated protein tau and paired helical filaments (PHF): demonstration at the electron microscope by a double immunogold labelling. Virchows Arch [A] 413:141–145

    Google Scholar 

  4. Delacourte A, Defossez A (1986) Alzheimer's disease: tau proteins, the promoting factors of microtubule assembly, are major antigenic components of paired helical filaments. J Neurol Sci 76:173–186

    Google Scholar 

  5. Delacourte A, Flament S, Defossez A, Buee L, Hemon B, Parent M, Furby A, Leys D, Goudemand M, Destee A, Petit H (1989) Tau 64 and 69: two early biochemical markers of the neurofibrillary degeneration. In: Boller F, Katzman R, Rascol A, Signoret J-L, Christen Y (eds) Colloques médecine et recherche: biological markers of Alzheimer's disease. Springer Verlag, Berlin Paris (in press)

    Google Scholar 

  6. Delaere P, Duyckaerts C, Brion JP, Poulain V, Hauw J-J (1989) Tau, paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in aging and senile dementia of Alzheimer type. Acta Neuropathol 77:645–653

    Google Scholar 

  7. Duyckaerts C, Hauw JJ, Piette F, Rainsard C, Poulain V, Berthaux P, Escourolle R (1985) Cortical atrophy in senile dementia of the Alzheimer type is mainly due to a decrease in cortical length. Acta Neuropathol (Berl) 66:72–74

    Google Scholar 

  8. Duyckaerts C, Hauw JJ, Bastenaire F, Piette F, Poulain V, Rainsard C, Javoy-Agid F, Berthaux P (1986) Laminar distribution of neocortical senile plaques in senile dementia of the Alzheimer type. Acta Neuropathol (Berl). 70:249–256

    Google Scholar 

  9. Duyckaerts C, Brion JP, Hauw JJ, Flament-Durand J (1987) Quantitative assessment of the density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. Comparison of immunocytochemistry with a specific antibody and Bodian's protargol method. Acta Neuropathol (Berl) 73:167–170

    Google Scholar 

  10. Duyckaerts C, Delaere P, Poulain V, Brion JP, Hauw JJ (1988) Does amyloid precede PHF in the senile plaque? A study of 15 cases with graded intellectual status in aging and AD. Neurosci Lett 91:354–359

    Google Scholar 

  11. Flament S, Delacourte A (1989) Abnormal tau species are produced during Alzheimer's disease neurodegenerating process. FEBS Lett 247:213–216

    Google Scholar 

  12. Flament S, Delacourte A, Hemon B, Defossez A (1989) Characterization of two pathological Tau protein variants in Alzheimer brain cortices. J Neurol Sci 92:133–141

    Google Scholar 

  13. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM (1986) Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J Biol Chem 261:6084–6089

    Google Scholar 

  14. Hansen LA, De Teresa R, Davies P, Terry RD (1988) Neocortical morphometry, lesion counts and choline acetyl-transferase levels in the age spectrum of AD. Neurology 38:48–54

    Google Scholar 

  15. Kemper Y (1984) Neuroanatomical and neuropathological changes in normal aging and dementia. In: Albert ML (ed) Clinical neurology of aging. Oxford University Press, New York, pp 9–52

    Google Scholar 

  16. Kidd M (1963) Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 197:192–193

    Google Scholar 

  17. Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubule-associated protein Tau is a major antigenic component of paired helical filaments in Alzheimer's disease. Proc Natl Acad Sci USA 83:4044–4048

    Google Scholar 

  18. Laemmli UK (1970) Cleavage of structural proteins during head assembly of bacteriophage T4 Nature 227:680–685

    Google Scholar 

  19. Moossy J, Zubenko GS, Martinez AJ, Rao GR (1988) Bilateral symetry of morphologic lesions in Alzheimer's disease. Arch Neurol 45:251–254

    Google Scholar 

  20. Nukina N, Ihara Y (1986) One of the antigenic determinants of paired helical filaments is related to Tau protein. J Biochem (Tokyo) 995:1541–1544

    Google Scholar 

  21. Parent M, Delacourte A, Defossez A, Hemon B, Han KK, Petit H (1988) Alzheimer's disease: study of the distribution of paired helical filaments Tau proteins in the human central nervous system. C R Acad Sci Paris 306:391–397

    Google Scholar 

  22. Wood JG, Mirra SS, Pollock NJ, Binder LI (1986) Neuro-fibrillary tangles of Alzheimer's disease share antigenic determinants with the axonal microtubule-associated protein Tau. Proc Natl Acad Sci USA 83:4040–4043

    Google Scholar 

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Supported by grants from MRES (88c.0710), CNMATS/NSERM and ADERMA

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Flament, S., Delacourte, A., Delaère, P. et al. Correlation between microscopical changes and Tau 64 and 69 biochemical detection in senile dementia of the Alzheimer type. Acta Neuropathol 80, 212–215 (1990). https://doi.org/10.1007/BF00308927

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  • DOI: https://doi.org/10.1007/BF00308927

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