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. 1985 Aug;120(2):292–303.

Monoclonal antibodies to Alzheimer neurofibrillary tangles. 2. Demonstration of a common antigenic determinant between ANT and neurofibrillary degeneration in progressive supranuclear palsy.

D W Dickson, Y Kress, A Crowe, S H Yen
PMCID: PMC1887828  PMID: 2411143

Abstract

Neurofibrillary degeneration is an argyrophilic intraneuronal lesion found in several unrelated neurologic conditions. The relationship between different types of neurofibrillary tangles is investigated with two monoclonal antibodies raised against Alzheimer neurofibrillary tangles (anti-ANT). Using the peroxidase-antiperoxidase technique, the authors demonstrate that neurofibrillary tangles of progressive supranuclear palsy, containing 15-nm straight filaments, share an antigenic determinant with ANTs. Ultrastructural studies localize the antigenic determinant to filamentous elements in the parakarya. The determinant is not present in normal brain, aluminum-induced experimental tangles in the rabbit, Lewy bodies, Hirano bodies, or axonal filamentous inclusions of amyotrophic lateral sclerosis and giant axonal neuropathy. It is, however, present in ANTs regardless of the pathologic condition in which they are found, including Alzheimer's disease, Down's syndrome, and postencephalitic Parkinson's disease.

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Selected References

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  1. Anderton B. H., Breinburg D., Downes M. J., Green P. J., Tomlinson B. E., Ulrich J., Wood J. N., Kahn J. Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature. 1982 Jul 1;298(5869):84–86. doi: 10.1038/298084a0. [DOI] [PubMed] [Google Scholar]
  2. Bignami A., Selkoe D. J., Dahl D. Amyloid-like (Congophilic) neurofibrillary tangles do not react with neurofilament antisera in Alzheimer's cerebral cortex. Acta Neuropathol. 1984;64(3):243–250. doi: 10.1007/BF00688115. [DOI] [PubMed] [Google Scholar]
  3. Brion J. P., Couck A. M., Flament-Durand J. Ultrastructural study of enriched fractions of "tangles" from human patients with senile dementia of the Alzheimer type. Acta Neuropathol. 1984;64(2):148–152. doi: 10.1007/BF00695578. [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., Shecket G. Immunological and silver staining characteristics of neurofibrillary tangles of Alzheimer type. Exp Brain Res. 1982;Suppl 5:15–19. doi: 10.1007/978-3-642-68507-1_3. [DOI] [PubMed] [Google Scholar]
  6. Gambetti P., Shecket G., Ghetti B., Hirano A., Dahl D. Neurofibrillary changes in human brain. An immunocytochemical study with a neurofilament antiserum. J Neuropathol Exp Neurol. 1983 Jan;42(1):69–79. doi: 10.1097/00005072-198301000-00006. [DOI] [PubMed] [Google Scholar]
  7. Ghetti B. Induction of neurofibrillary degeneration following treatment with maytansine in vivo. Brain Res. 1979 Mar 9;163(1):9–19. doi: 10.1016/0006-8993(79)90147-1. [DOI] [PubMed] [Google Scholar]
  8. Goldman J. E. The association of actin with Hirano bodies. J Neuropathol Exp Neurol. 1983 Mar;42(2):146–152. doi: 10.1097/00005072-198303000-00004. [DOI] [PubMed] [Google Scholar]
  9. Goldman J. E., Yen S. H., Chiu F. C., Peress N. S. Lewy bodies of Parkinson's disease contain neurofilament antigens. Science. 1983 Sep 9;221(4615):1082–1084. doi: 10.1126/science.6308771. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Grundke-Iqbal I., Johnson A. B., Terry R. D., Wisniewski H. M., Iqbal K. Alzheimer neurofibrillary tangles: antiserum and immunohistological staining. Ann Neurol. 1979 Dec;6(6):532–537. doi: 10.1002/ana.410060612. [DOI] [PubMed] [Google Scholar]
  12. Hirano A., Dembitzer H. M., Kurland L. T., Zimmerman H. M. The fine structure of some intraganglionic alterations. Neurofibrillary tangles, granulovacuolar bodies and "rod-like" structures as seen in Guam amyotrophic lateral sclerosis and parkinsonism-dementia complex. J Neuropathol Exp Neurol. 1968 Apr;27(2):167–182. [PubMed] [Google Scholar]
  13. Hirano A., Donnenfeld H., Sasaki S., Nakano I. Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 1984 Sep;43(5):461–470. doi: 10.1097/00005072-198409000-00001. [DOI] [PubMed] [Google Scholar]
  14. Horoupian D. S., Yang S. S. Paired helical filaments in neurovisceral lipidosis (juvenile dystonic lipidosis). Ann Neurol. 1978 Nov;4(5):404–411. doi: 10.1002/ana.410040504. [DOI] [PubMed] [Google Scholar]
  15. Ishii T., Nakamura Y. Distribution and ultrastructure of Alzheimer's neurofibrillary tangles in postencephalitic Parkinsonism of Economo type. Acta Neuropathol. 1981;55(1):59–62. doi: 10.1007/BF00691532. [DOI] [PubMed] [Google Scholar]
  16. Ishino H., Otsuki S. Frequency of Alzheimer's neurofibrillary tangles in the cerebral cortex in progressive supranuclear palsy (subcortical argyrophilic dystrophy). J Neurol Sci. 1976 Jul;28(3):309–316. doi: 10.1016/0022-510x(76)90024-1. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Munoz-Garcia D., Ludwin S. K. Classic and generalized variants of Pick's disease: a clinicopathological, ultrastructural, and immunocytochemical comparative study. Ann Neurol. 1984 Oct;16(4):467–480. doi: 10.1002/ana.410160408. [DOI] [PubMed] [Google Scholar]
  19. Pickel V. M., Joh T. H., Reis D. J. Monoamine-synthesizing enzymes in central dopaminergic, noradrenergic and serotonergic neurons. Immunocytochemical localization by light and electron microscopy. J Histochem Cytochem. 1976 Jul;24(7):792–306. doi: 10.1177/24.7.8567. [DOI] [PubMed] [Google Scholar]
  20. Prineas J. W., Ouvrier R. A., Wright R. G., Walsh J. C., McLeod J. G. Gian axonal neuropathy--a generalized disorder of cytoplasmic microfilament formation. J Neuropathol Exp Neurol. 1976 Jul;35(4):458–470. doi: 10.1097/00005072-197607000-00006. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Roy S., Datta C. K., Hirano A., Ghatak N. R., Zimmerman H. M. Electron microscopic study of neurofibrillary tangles in Steele-Richardson-Olszewski syndrome. Acta Neuropathol. 1974;29(2):175–179. doi: 10.1007/BF00684775. [DOI] [PubMed] [Google Scholar]
  23. STEELE J. C., RICHARDSON J. C., OLSZEWSKI J. PROGRESSIVE SUPRANUCLEAR PALSY. A HETEROGENEOUS DEGENERATION INVOLVING THE BRAIN STEM, BASAL GANGLIA AND CEREBELLUM WITH VERTICAL GAZE AND PSEUDOBULBAR PALSY, NUCHAL DYSTONIA AND DEMENTIA. Arch Neurol. 1964 Apr;10:333–359. doi: 10.1001/archneur.1964.00460160003001. [DOI] [PubMed] [Google Scholar]
  24. Schwartz P. Amyloid degeneration and tuberculosis in the aged. Gerontologia. 1972;18(5-6):321–362. doi: 10.1159/000211943. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. TERRY R. D., PENA C. EXPERIMENTAL PRODUCTION OF NEUROFIBRILLARY DEGENERATION 2. ELECTRON MICROSCOPY, PHOSPHATASE HISTOCHEMISTRY AND ELECTRON PROBE ANALYSIS. J Neuropathol Exp Neurol. 1965 Apr;24:200–210. doi: 10.1097/00005072-196504000-00003. [DOI] [PubMed] [Google Scholar]
  29. Takauchi S., Mizuhara T., Miyoshi K. Unusual paired helical filaments in progressive supranuclear palsy. Acta Neuropathol. 1983;59(3):225–228. doi: 10.1007/BF00703207. [DOI] [PubMed] [Google Scholar]
  30. Tellez-Nagel I., Wiśniewski H. M. Ultrastructure of neurofibrillary tangles in Steele-Richardson-Olszewski syndrome. Arch Neurol. 1973 Nov;29(5):324–327. doi: 10.1001/archneur.1973.00490290064007. [DOI] [PubMed] [Google Scholar]
  31. Terry R. D., Katzman R. Senile dementia of the Alzheimer type. Ann Neurol. 1983 Nov;14(5):497–506. doi: 10.1002/ana.410140502. [DOI] [PubMed] [Google Scholar]
  32. Tomlinson B. E., Blessed G., Roth M. Observations on the brains of non-demented old people. J Neurol Sci. 1968 Sep-Oct;7(2):331–356. doi: 10.1016/0022-510x(68)90154-8. [DOI] [PubMed] [Google Scholar]
  33. Tomonaga M. Hirano body in extraocular muscle. Acta Neuropathol. 1983;60(3-4):309–313. doi: 10.1007/BF00691883. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Wisniewski K., Jervis G. A., Moretz R. C., Wisniewski H. M. Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia. Ann Neurol. 1979 Mar;5(3):288–294. doi: 10.1002/ana.410050311. [DOI] [PubMed] [Google Scholar]
  36. Wiśniewski H. M., Coblentz J. M., Terry R. D. Pick's disease. A clinical and ultrastructural study. Arch Neurol. 1972 Feb;26(2):97–108. doi: 10.1001/archneur.1972.00490080015001. [DOI] [PubMed] [Google Scholar]
  37. Wiśniewski H., Terry R. D., Hirano A. Neurofibrillary pathology. J Neuropathol Exp Neurol. 1970 Apr;29(2):163–176. [PubMed] [Google Scholar]
  38. Yagishita S., Itoh Y., Amano N., Nakano T., Saitoh A. Ultrastructure of neurofibrillary tangles in progressive supranuclear palsy. Acta Neuropathol. 1979 Oct;48(1):27–30. doi: 10.1007/BF00691787. [DOI] [PubMed] [Google Scholar]
  39. Yagishita S., Itoh Y., Nan W., Amano N. Reappraisal of the fine structure of Alzheimer's neurofibrillary tangles. Acta Neuropathol. 1981;54(3):239–246. doi: 10.1007/BF00687747. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Yen S. H., Horoupian D. S., Terry R. D. Immunocytochemical comparison of neurofibrillary tangles in senile dementia of Alzheimer type, progressive supranuclear palsy, and postencephalitic parkinsonism. Ann Neurol. 1983 Feb;13(2):172–175. doi: 10.1002/ana.410130211. [DOI] [PubMed] [Google Scholar]

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