Advertisement

Immunocytochemical and ultrastructural pathology of nerve cells in Alzheimer’s disease and related disorders

  • H. Lassmann
  • P. Fischer
  • C. Bancher
  • K. Jellinger
Part of the Key Topics in Brain Research book series (KEYTOPICS)

Summary

Neurofibrillary tangles in Alzheimer’s disease were analysed by light and electron microscopic immunocytochemistry using antibodies against cytoskeletal antigens and ubiquitin. Our studies indicate that the antigenicity of paired helical filaments is profoundly changed during the stages of tangle formation and maturation. In addition, tangle formation may lead to changes in other neuronal cytoskeletal elements. A comparison of Alzheimer neurofibrillary tangles with cytoplasmic fibrillary inclusions in other CNS diseases indicates that ubiquitin binding to abnormal proteins may be a common denominator of such cytopathological conditions.

Keywords

Neurofibrillary Tangle Alcian Blue Progressive Supranuclear Palsy Paired Helical Filament Antigenic Profile 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatrie 64: 107Google Scholar
  2. Alzheimer A (1911) Über eigenartige Krankheitsfälle des späten Alters. Z Ges Neurol Psychiatr 4: 356–385CrossRefGoogle Scholar
  3. Anderton BH, Breinburg D, Downes MJ, Green PJ, Tomlinson BE, Ulrich J, Wood JN, Kahn J (1982) Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature 298: 84–86PubMedCrossRefGoogle Scholar
  4. Bancher C, Lassmann H, Budka H, Grundke Iqbal I, Iqbal K, Wiche G, Seitelberger F, Wisniewski HM (1987) Neurofibrillary tangles in Alzheimer’s disease and progressive supranuclear palsy: antigenic similarities and differences. Acta Neuropathol (Berl) 74: 39–46CrossRefGoogle Scholar
  5. Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke Iqbal I, Iqbal K, Wisniewski HM (1989a) Accumulation of phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer’s disease. Brain Res 477: 90–99PubMedCrossRefGoogle Scholar
  6. Bancher C, Lassmann H, Budka H, Jellinger K, Grundke Igbal I, Iqbal K, Wiche G, Seitelberger F, Wisniewski HM (1989b) An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination. J Neuropathol Exp Neurol 48: 81–93PubMedCrossRefGoogle Scholar
  7. Brion JP, Passarier H, Nunez J, Flament-Durand J (1985) Immunologic determinants of tau protein are present in neurofibrillary tangles. Arch Biol 95: 229–235Google Scholar
  8. Brunner C, Lassmann H, Waehnelt TV, Matthieu JM, Linington C (1989) Differential ultrastructural localization of myelin basic protein, myelin/oligodendroglial glycoprotein and 2,3-cyclic nucleoside 3-phosphodiesterase in the CNS of adult rats. J Neurochem 52: 296–304PubMedCrossRefGoogle Scholar
  9. Defossez A, Delacourte A (1987) Transformation of degenerating neurofibrils into amyloid substance in Alzheimer’s disease: histochemical and immunohistochemical studies. J Neurol Sci 81: 1–10PubMedCrossRefGoogle Scholar
  10. Delaere P, Duyckaerts C, Brion JP, Poulain V, Hauw JJ (1989) Tau, paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in ageing and senile dementia of Alzheimer type. Acta Neuropathol (Berl) 77: 645–653CrossRefGoogle Scholar
  11. Fischer P, Gatterer G, Marterer A, Danielczyk W (1988) Non specificity of semantic impairment in dementia of Alzheimer’s type. Arch Neurol 45: 1341–1343PubMedCrossRefGoogle Scholar
  12. Grundke lgbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule associated protein tau in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83: 4913–4917CrossRefGoogle Scholar
  13. Hyman BT, Van Hoesen GW, Woloczin B, Davis P, Kromer LJ, Damasio AR (1987) Alz 50 antibody recognizes Alzheimer-related neuronal changes. Ann Neurol 23: 371–379CrossRefGoogle Scholar
  14. Ihara Y, Abraham C, Selkoe DJ (1983) Antibodies to paired helical filaments do not recognize normal brain proteins. Nature 304: 727–730PubMedCrossRefGoogle Scholar
  15. Joachim CL, Morris JH, Selkoe DJ, Kosik KS (1987) Tau epitopes are incorporated into a range of lesions in Alzheimer’s disease. J Neuropathol Exp Neurol 46: 611–622PubMedCrossRefGoogle Scholar
  16. Kosik KS, Duffy LK, Dowling MM, Abraham C, McCluskey A, Selkoe DJ (1984) Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes in Alzheimer neurofibrillary tangles. Proc Natl Acad Sci USA 81: 7941–7945PubMedCrossRefGoogle Scholar
  17. Ksiezak-Reding H, Binder LI, Yen SH (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: 7948–7953PubMedGoogle Scholar
  18. Ksiezak-Reding H, Davis P, Yen SH (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: 7943–7947PubMedGoogle Scholar
  19. Manetto V, Perry G, Tabaton M, Mulvihill P, Fried V, Smith H, Gambetti P, Autilio-Gambetti L (1988) Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative disease. Proc Natl Acad Sci USA 85: 4501–4505PubMedCrossRefGoogle Scholar
  20. Masters CL, Multhaup G, Simms G, Pottglesser J, Martins RN, Beyreuther K (1985) Neuronal origin of cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4: 2757–2763PubMedGoogle Scholar
  21. Mori H, Kondo J, Ihara Y (1987) Ubiquitin is a component of paired helical filaments. Science 235: 1641–1644PubMedCrossRefGoogle Scholar
  22. Nukina N, Kosik KS, Selkoe DJ (1988) The monoclonal antibody, Alz 50, recognizes tau proteins in Alzheimer’s disease brain. Neurosci Lett 87: 240–246PubMedCrossRefGoogle Scholar
  23. Perry G, Friedmann R, Shaw G, Chau V (1987) Ubiquitin is detected in neurofibrillary tangles and senile plaque neuntes of Alzheimer disease brains. Proc Natl Acad Sci USA 84: 3033–3036PubMedCrossRefGoogle Scholar
  24. Perry G, Mulvihil P, Fried VA, Smith HT, Grundke Iqbal I, Iqbal K (1989) Immunochemical properties of ubiquitin conjugates in the paired helical filaments of Alzheimer’s disease. J Neurochem 52: 1523–1528PubMedCrossRefGoogle Scholar
  25. Probst A, Ulrich J, Heitz PU (1982) Senile dementia of Alzheimer type: astroglial reaction to extracellular neurofibrillary tangles in the hippocampus. An immunohistochemical and electron-microscopic study. Acta Neuropathol (Berl) 57: 75–79CrossRefGoogle Scholar
  26. Snow AD, Willmer JP, Kisilewski R (1987) Sulphated glycosaminoglycans in Alzheimer’s disease. Hum Pathol 18: 506–510PubMedCrossRefGoogle Scholar
  27. Sternberger NH, Sternberger LA, Ulrich J (1985) Aberrant neurofilament phosphorylation in Alzheimer disease. Proc Natl Acad Sci 82: 4274–4276PubMedCrossRefGoogle Scholar
  28. Szumanska G, Vorbrodt AW, Mandybur TI, Wisniewski HM (1987) Lectin histochemistry of plaques and tangles in Alzheimer’s disease. Acta Neuropathol 73: 1–11PubMedCrossRefGoogle Scholar
  29. Vass K, Iassmann H, Wekerle H, Wisniewski HM (1986) The distribution of Ia-antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol 70: 149–160PubMedCrossRefGoogle Scholar
  30. Wang GP, Grundke Iqbal I, Kascak RJ, Igbal K, Wisniewski HM (1984) Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s). Acta Neuropathol 62: 268–275PubMedCrossRefGoogle Scholar
  31. Wischik CM, Novak M, Thogersen HL, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988) Isolation of a fragment of tau derived from the core of paired helical filament of Alzheimer’s disease. Proc Natl Acad Sci USA 85: 4506–4510PubMedCrossRefGoogle Scholar
  32. Wolozin BL, Bruchnicki A, Dickson DW, Davis P (1986) A neuronal antigen in the brains of Alzheimer patients. Science 232: 648–650PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1990

Authors and Affiliations

  • H. Lassmann
    • 1
  • P. Fischer
    • 1
    • 2
  • C. Bancher
    • 1
    • 4
  • K. Jellinger
    • 3
  1. 1.Neurological InstituteUniversity of ViennaViennaAustria
  2. 2.Institute of Brain ResearchAustrian Academy of ScienceViennaAustria
  3. 3.Ludwig Boltzmann Institute for Clinical NeurobiologyLainz Geriatric HospitalViennaAustria
  4. 4.New York State Institute for Basic Research in Developmental DisabilitiesNew YorkUSA

Personalised recommendations