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J Cell Biol. 1985 June 1; 100(6): 1905–1912.
PMCID: PMC2113596

Subunit structure of paired helical filaments in Alzheimer's disease


The neurofibrillary tangles that occur in the brain in cases of senile dementia of the Alzheimer type contain a distinctive type of filament, the paired helical filament (PHF). We have developed a method for isolating the tangles postmortem in sufficient yield for structural study of PHFs by electron microscopy of negatively stained and shadowed preparations. This material shows the characteristic helical structure seen in sectioned embedded material. In addition, two striking fragmentation patterns are observed. (a) Some filaments show sharp transverse breaks at apparently random positions along the filament. (b) In a few PHFs one strand is missing for a variable length, whereas the other appears to maintain its structural integrity. The shadowed specimens show the PHF to be wound in a left-handed manner. These observations indicate that the PHF consists of subunits of very limited axial extent arranged along two left-handed helical strands. The visualization of the substructure within the PHFs is rather variable and a model building approach has therefore been adopted, which has allowed the main features seen in the images to be interpreted. The subunit appears to have at least two domains in a radial direction and an axial extent of less than 5 nm. The whole structure can best be described as a twisted ribbon and indeed alkali treatment does untwist PHFs to give flat ribbons. The nature of the proposed model makes it most unlikely that the PHF is formed by a simple collapse of normal cytoskeletal elements, such as neurofilaments.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aebi U, Fowler WE, Rew P, Sun TT. The fibrillar substructure of keratin filaments unraveled. J Cell Biol. 1983 Oct;97(4):1131–1143. [PMC free article] [PubMed]
  • Anderton BH, Breinburg D, Downes MJ, Green PJ, Tomlinson BE, Ulrich J, Wood JN, Kahn J. Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature. 1982 Jul 1;298(5869):84–86. [PubMed]
  • Blessed G, Tomlinson BE, Roth M. The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry. 1968 Jul;114(512):797–811. [PubMed]
  • 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. [PubMed]
  • KIDD M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature. 1963 Jan 12;197:192–193. [PubMed]
  • Ihara Y, Abraham C, Selkoe DJ. Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature. 1983 Aug 25;304(5928):727–730. [PubMed]
  • Metuzals J, Montpetit V, Clapin DF. Organization of the neurofilamentous network. Cell Tissue Res. 1981;214(3):455–482. [PubMed]
  • Roth M, Tomlinson BE, Blessed G. The relationship between quantitative measures of dementia and of degenerative changes in the cerebral grey matter of elderly subjects. Proc R Soc Med. 1967 Mar;60(3):254–260. [PMC free article] [PubMed]
  • Selkoe DJ, Liem RK, Yen SH, Shelanski ML. Biochemical and immunological characterization of neurofilaments in experimental neurofibrillary degeneration induced by aluminum. Brain Res. 1979 Mar 16;163(2):235–252. [PubMed]
  • Selkoe DJ, Abraham C, Ihara Y. Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6070–6074. [PubMed]
  • Shaw G, Osborn M, Weber K. An immunofluorescence microscopical study of the neurofilament triplet proteins, vimentin and glial fibrillary acidic protein within the adult rat brain. Eur J Cell Biol. 1981 Dec;26(1):68–82. [PubMed]
  • Tomlinson BE. The pathology of dementia. Contemp Neurol Ser. 1977;15:113–153. [PubMed]
  • Wais-Steider C, Eagles PA, Gilbert DS, Hopkins JM. Structural similarities and differences amongst neurofilaments. J Mol Biol. 1983 Apr 5;165(2):393–400. [PubMed]
  • Wang GP, Grundke-Iqbal I, Kascsak RJ, Iqbal K, Wisniewski HM. Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s). Acta Neuropathol. 1984;62(4):268–275. [PubMed]
  • Wilcock GK, Esiri MM. Plaques, tangles and dementia. A quantitative study. J Neurol Sci. 1982 Nov;56(2-3):343–356. [PubMed]
  • Wiśniewski HM, Narang HK, Terry RD. Neurofibrillary tangles of paired helical filaments. J Neurol Sci. 1976 Feb;27(2):173–181. [PubMed]
  • Wisniewski K, Jervis GA, Moretz RC, Wisniewski HM. Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia. Ann Neurol. 1979 Mar;5(3):288–294. [PubMed]
  • Wisniewski HM, Merz PA, Iqbal K. Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle. J Neuropathol Exp Neurol. 1984 Nov;43(6):643–656. [PubMed]
  • 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. [PubMed]
  • Yen SH, Gaskin F, Terry RD. Immunocytochemical studies of neurofibrillary tangles. Am J Pathol. 1981 Jul;104(1):77–89. [PubMed]

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