Senile plaque neurites fail to demonstrate anti-paired helical filament and anti-microtubule-associated protein-tau immunoreactive proteins in the absence of neurofibrillary tangles in the neocortex (original) (raw)

Summary

Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired helical filaments (PHF) have long been documented in SP neurites, we do not know if they are of pathogenetic relevance for the formation of the SP. To investigate the relationship between NFT and SP, we examined antigenic properties of proteins in SP neurites in neocortical tissues of patients with senile dementia of Alzheimer type, in the presence or absence of NFT in the same cortical area. We used two polyclonal antibodies directed against PHF and microtubule-associated protein (MAP)-tau and three monoclonal antibodies (MAbs) (RT97, BF10, 147) to phosphorylated epitopes of human neurofilament polypeptides, as well as the Gallyas silver impregnation method which specifically stains PHF in NFT and neurites. The main finding of our investigations consists in a differential pattern of immunoreactivity of SP neurites depending on the presence or absence of NFT in the neocortex. In the presence of NFT, there were numerous neuropil threads and SP neurites containing Gallyas-positive, as well as anti-PHF- and anti-tau-labelled material. In the absence of NFT in the neocortex there was a striking absence of any Gallyas-positive or PHF- and tau-immunoreactive structure in the cortical neuropil and in SP neurites, irrespective of the maturation stage of the SP. In contrast with these results, the number of neurites labelled by MAbs RT97, BF10 and 147 in SP and in the neuropil was apparently unaffected by the presence or absence of NFT. Amyloid in SP, remained consistently unstained by all antibodies of the panel as well as by the Gallyas stain. Our findings indicate that PHF and tau polypeptides are facultative components of SP neurites and suggest that the development of SP may occur independently of PHF pathology in neocortical neurons.

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References

  1. Allsop D, Landon M, Kidd M, Lowe JS, Reynolds SP, Garnier A (1986) Monoclonal antibodies raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease. Neurosci Lett 68;252–256
    Google Scholar
  2. 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: 84–86
    Google Scholar
  3. Braak H, Braak E, Iqbal IG, Iqbal K (1986), Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65:351–355
    Google Scholar
  4. Brion JP, Couck AM, Passareiro E, Flament-Durant J (1985) Neurofibrillary tangles of Alzheimer's disease: an immunohistochemical study. J Submicrosc Cytol 17:89–96
    Google Scholar
  5. Brion JP, Passareiro H, Nunez J, Flament-Durand J (1985) Mise en évidence imunologique de la proteine tau au niveau des lésions de dégénérescence neurofibrillaire de la maladie d'Alzheimer. Arch Biol 95:229–235
    Google Scholar
  6. Folstein FM, Folstein SE, McHugh PR (1975) Mini-mental test: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1:189–198
    Google Scholar
  7. Gallyas F (1987) Silver staining of Alzheimer's neurofibrillary changes by means of physical development. Acta Morphol Acad Sci Hung 19:1–8
    Google Scholar
  8. Gonatas NK, Anderson W, Evangelista I (1967) The contribution of altered synapses in the senile plaque: an electron microscopic study in Alzheimer's dementia. J Neuropathol Exp Neurol 26:29–39
    Google Scholar
  9. Haugh MC, Probst A, Ulrich J, Kahn J, Anderton BH (1986) Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes. J Neurol Neurosurg Psychiatry 49:1212–1220
    Google Scholar
  10. Iqbal GI, Iqbal K, Tung YC, Wisniewski HM (1984) Alzheimer paired helical filaments: immunochemical identification of polypeptides. Acta Neuropathol (Berl) 62:259–267
    Google Scholar
  11. Iqbal GI, 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 83:4913–4917
    Google Scholar
  12. Iqbal K, Iqbal IG, Wisniewski H (1987) A silver impregnation method specific for Alzheimer paired helical filaments (PHF) stains microtubule associated protein Tau. J Neuropathol Exp Neurol (Abstr) 46:333
    Google Scholar
  13. Kahn J, Geon PG, Thorpe R, Anderton BH (1980) Immunohistochemistry of neurofilaments in Alzheimer's disease. J Clin Exp Gerontol 2:199–210
    Google Scholar
  14. Khachaturian ZS (1985) Diagnosis of Alzheimer's disease. Arch Neurol 42:1097–1104
    Google Scholar
  15. Kosik KS, Joachim CL, Selkoe DJ (1986) The microtubuleassociated 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
  16. Kowall NW, Kosik KS (1987) Axonal disruption and aberrant localization of tau protein characterize neuropil pathology of Alzheimer's disease. Ann Neurol 22:639–643
    Google Scholar
  17. Masters CL, Multhaup G, Simms G, Pottgiesser 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 4:2757–2763
    Google Scholar
  18. Probst A, Basler V, Bron B, Ulrich J (1983) Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region. Brain Res 268:249–254
    Google Scholar
  19. Probst A, Brunnschweiler H, Lautenschalager C, Ulrich J (1987) A special type of senile plaque, possibly an initial stage. Acta Neuropathol (Berl) 74:133–141
    Google Scholar
  20. Schwartz P (1970) Amyloidosis: cause and manifestation of senile deterioration. Thomas (ed). Springfield, Illinois
  21. Selkoe DJ, Abraham CR, Podlisny B, Duffy LK (1986) Isolation of low-molecular weight proteins from amyloid plaque fibers in Alzheimer's disease. J Neurochem 146: 1820–1834
    Google Scholar
  22. Terry RD, Hansen LA, De Teresa R, Davies P, Tobias H, Katzman R (1987) Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp., Neurol 46:262–268
    Google Scholar
  23. 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. Plenum, New York, pp 165–142
    Google Scholar

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Authors and Affiliations

  1. Department of Pathology, Division of Neuropathology, University of Basel, Switzerland
    A. Probst & J. Ulrich
  2. Department of Immunology, St George's Hospital Medical School, Cranmer Terrace, SW17 0RE, London, UK
    B. H. Anderton
  3. Laboratoire d'Anatomie Pathologique et de Microscopie éléctronique, Université Libre de Bruxelles, Belgique
    J. -P. Brion

Authors

  1. A. Probst
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  2. B. H. Anderton
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  3. J. -P. Brion
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  4. J. Ulrich
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Supported by the Wellcome Trust and the Medical Research Council

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Probst, A., Anderton, B.H., Brion, J.P. et al. Senile plaque neurites fail to demonstrate anti-paired helical filament and anti-microtubule-associated protein-tau immunoreactive proteins in the absence of neurofibrillary tangles in the neocortex.Acta Neuropathol 77, 430–436 (1989). https://doi.org/10.1007/BF00687379

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