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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1986 Nov;49(11):1213–1220. doi: 10.1136/jnnp.49.11.1213

Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes.

M C Haugh, A Probst, J Ulrich, J Kahn, B H Anderton
PMCID: PMC1029067  PMID: 2432188

Abstract

Three monoclonal antibodies to neurofilaments (RT97, BF10 and 147), two of which also recognised neurofibrillary tangles (RT97 and BF10), have all been shown to be specific for phosphorylated epitopes. Treatment of histological sections with alkaline phosphatase prior to immunostaining resulted in reduction of axonal neurofilament staining with all three whilst the neurofibrillary tangles staining with BF10 was unaffected. Antibody 147 was found to recognise weakly some neurofibrillary tangles following alkaline phosphatase treatment. The results presented confirm the presence of structurally abnormal but phosphorylated neurofilaments in neurofibrillary tangles.

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Selected References

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  1. Anderton B. H., Thorpe R., Cohen J., Selvendran S., Woodhams P. Specific neuronal localization by immunofluorescence of 10 nm filament polypeptides. J Neurocytol. 1980 Dec;9(6):835–844. doi: 10.1007/BF01205022. [DOI] [PubMed] [Google Scholar]
  2. Brion J. P., Couck A. M., Passareiro E., Flament-Durand J. Neurofibrillary tangles of Alzheimer's disease: an immunohistochemical study. J Submicrosc Cytol. 1985 Jan;17(1):89–96. [PubMed] [Google Scholar]
  3. Dräger U. C., Hofbauer A. Antibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina. Nature. 1984 Jun 14;309(5969):624–626. doi: 10.1038/309624a0. [DOI] [PubMed] [Google Scholar]
  4. Elovaara I., Paetau A., Lehto V. P., Dahl D., Virtanen I., Palo J. Immunocytochemical studies of Alzheimer neuronal perikarya with intermediate filament antisera. J Neurol Sci. 1983 Dec;62(1-3):315–326. doi: 10.1016/0022-510x(83)90208-3. [DOI] [PubMed] [Google Scholar]
  5. Gambetti P., Autilio-Gambetti L., Perry G., Shecket G., Crane R. C. Antibodies to neurofibrillary tangles of Alzheimer's disease raised from human and animal neurofilament fractions. Lab Invest. 1983 Oct;49(4):430–435. [PubMed] [Google Scholar]
  6. Grundke-Iqbal I., Iqbal K., Tung Y. C., Wisniewski H. M. Alzheimer paired helical filaments: immunochemical identification of polypeptides. Acta Neuropathol. 1984;62(4):259–267. doi: 10.1007/BF00687607. [DOI] [PubMed] [Google Scholar]
  7. Grundke-Iqbal I., Johnson A. B., Wisniewski H. M., Terry R. D., Iqbal K. Evidence that Alzheimer neurofibrillary tangles originate from neurotubules. Lancet. 1979 Mar 17;1(8116):578–580. doi: 10.1016/s0140-6736(79)91006-7. [DOI] [PubMed] [Google Scholar]
  8. Hirokawa N., Glicksman M. A., Willard M. B. Organization of mammalian neurofilament polypeptides within the neuronal cytoskeleton. J Cell Biol. 1984 Apr;98(4):1523–1536. doi: 10.1083/jcb.98.4.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ihara Y., Abraham C., Selkoe D. J. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature. 1983 Aug 25;304(5928):727–730. doi: 10.1038/304727a0. [DOI] [PubMed] [Google Scholar]
  10. Iqbal K., Zaidi T., Thompson C. H., Merz P. A., Wisniewski H. M. Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition. Acta Neuropathol. 1984;62(3):167–177. doi: 10.1007/BF00691849. [DOI] [PubMed] [Google Scholar]
  11. Julien J. P., Mushynski W. E. Multiple phosphorylation sites in mammalian neurofilament polypeptides. J Biol Chem. 1982 Sep 10;257(17):10467–10470. [PubMed] [Google Scholar]
  12. Julien J. P., Mushynski W. E. The distribution of phosphorylation sites among identified proteolytic fragments of mammalian neurofilaments. J Biol Chem. 1983 Mar 25;258(6):4019–4025. [PubMed] [Google Scholar]
  13. KIDD M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature. 1963 Jan 12;197:192–193. doi: 10.1038/197192b0. [DOI] [PubMed] [Google Scholar]
  14. Kosik K. S., Duffy L. K., Dowling M. M., Abraham C., McCluskey A., Selkoe D. J. Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7941–7945. doi: 10.1073/pnas.81.24.7941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Probst A., Anderton B. H., Ulrich J., Kohler R., Kahn J., Heitz P. U. Pick's disease: an immunocytochemical study of neuronal changes. Monoclonal antibodies show that Pick bodies share antigenic determinants with neurofibrillary tangles and neurofilaments. Acta Neuropathol. 1983;60(3-4):175–182. doi: 10.1007/BF00691864. [DOI] [PubMed] [Google Scholar]
  17. Rasool C. G., Abraham C., Anderton B. H., Haugh M., Kahn J., Selkoe D. J. Alzheimer's disease: immunoreactivity of neurofibrillary tangles with anti-neurofilament and anti-paired helical filament antibodies. Brain Res. 1984 Sep 24;310(2):249–260. doi: 10.1016/0006-8993(84)90148-3. [DOI] [PubMed] [Google Scholar]
  18. Rasool C. G., Selkoe D. J. Alzheimer's disease: exposure of neurofilament immunoreactivity in SDS-insoluble paired helical filaments. Brain Res. 1984 Nov 19;322(1):194–198. doi: 10.1016/0006-8993(84)91205-8. [DOI] [PubMed] [Google Scholar]
  19. Selkoe D. J., Ihara Y., Salazar F. J. Alzheimer's disease: insolubility of partially purified paired helical filaments in sodium dodecyl sulfate and urea. Science. 1982 Mar 5;215(4537):1243–1245. doi: 10.1126/science.6120571. [DOI] [PubMed] [Google Scholar]
  20. Sharp G. A., Shaw G., Weber K. Immunoelectronmicroscopical localization of the three neurofilament triplet proteins along neurofilaments of cultured dorsal root ganglion neurones. Exp Cell Res. 1982 Feb;137(2):403–413. doi: 10.1016/0014-4827(82)90042-8. [DOI] [PubMed] [Google Scholar]
  21. Sternberger L. A., Sternberger N. H. Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6126–6130. doi: 10.1073/pnas.80.19.6126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wang G. P., Grundke-Iqbal I., Kascsak R. J., Iqbal K., Wisniewski H. M. Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s). Acta Neuropathol. 1984;62(4):268–275. doi: 10.1007/BF00687608. [DOI] [PubMed] [Google Scholar]
  24. Wilcock G. K., Esiri M. M., Bowen D. M., Smith C. C. Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J Neurol Sci. 1982 Dec;57(2-3):407–417. doi: 10.1016/0022-510x(82)90045-4. [DOI] [PubMed] [Google Scholar]
  25. Wischik C. M., Crowther R. A., Stewart M., Roth M. Subunit structure of paired helical filaments in Alzheimer's disease. J Cell Biol. 1985 Jun;100(6):1905–1912. doi: 10.1083/jcb.100.6.1905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wiśniewski H. M., Narang H. K., Terry R. D. Neurofibrillary tangles of paired helical filaments. J Neurol Sci. 1976 Feb;27(2):173–181. doi: 10.1016/0022-510x(76)90059-9. [DOI] [PubMed] [Google Scholar]
  27. Wiśniewski H., Terry R. D., Hirano A. Neurofibrillary pathology. J Neuropathol Exp Neurol. 1970 Apr;29(2):163–176. [PubMed] [Google Scholar]
  28. Yen S. H., Gaskin F., Fu S. M. Neurofibrillary tangles in senile dementia of the Alzheimer type share an antigenic determinant with intermediate filaments of the vimentin class. Am J Pathol. 1983 Dec;113(3):373–381. [PMC free article] [PubMed] [Google Scholar]
  29. Yen S. H., Gaskin F., Terry R. D. Immunocytochemical studies of neurofibrillary tangles. Am J Pathol. 1981 Jul;104(1):77–89. [PMC free article] [PubMed] [Google Scholar]

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