Skip to main content
Log in

Alzheimer paired helical filaments: a comparison with the twisted ribbon model

  • Short Original Communication
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

To investigate if Alzheimer paired helical filaments (PHF) closely resemble twisted ribbons, as indicated by recent high-resolution ultrastructural studies, we compared physical models of twisted ribbons with electron microscopic images of PHF. Uranyl-acetate-stained, isolated PHF with one or two helical turns were compared with scale models of twisted ribbons with one and two helical turns rotated at different angles. The various rotations of the twisted ribbon model corresponded well with the different orientations of randomly dispersed PHF. The electron-dense regions of individual PHF turns previously thought to represent a cross-over site of paired filaments corresponded to the edge of the twisted ribbon when the ribbon was oriented perpendicular to the filament axis. These data indicate that the overall configuration of PHF is a twisted ribbon but does not exclude possible configuration restrictions due to an ordered arrangement of subunits.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Appelt DM, Balin BJ (1993) Analysis of paired helical filaments (PHF) found in Alzheimer's disease using freeze-drying/rotary shadowing. J Struct Biol 111: 85–95

    Google Scholar 

  2. Crowther RA (1991) Straight and paired helical filaments in Alzheimer's disease have a common structural unit. Proc Natl Acad Sci USA 88: 2288–2292

    Google Scholar 

  3. Crowther RA, Wischik CM (1985) Image reconstruction of the Alzheimer paired helical filament. EMBO J 4: 3661–3665

    Google Scholar 

  4. Crowther RA, Olesen OF, Smith MJ, Goedert M (1994) Assembly of Alzheimer-like filaments from full-length tau protein. FEBS Lett 337: 135–138

    Google Scholar 

  5. Greenberg SC, Davies P (1990) A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 87: 5827–5831

    Google Scholar 

  6. Grundke-Iqbal I, Iqbal K, Tung Y-C, 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 

  7. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung Y-C, Zaidi MS, Wisniewski HM (1986) Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J Biol Chem 261: 6084–6089

    Google Scholar 

  8. Kidd M (1963) Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 197: 192–193

    Google Scholar 

  9. Kidd M (1964) Alzheimer's disease — an electron microscopical study. Brain 87: 307–320

    Google Scholar 

  10. Kirschner DA, Abraham C, Selkoe D (1986) X-ray diffraction from intraneuronal paired helical filaments and extraneuronal amyloid fibers in Alzheimer disease indicates cross-\ conformation. Proc Natl Acad Sci USA 83: 503–507

    Google Scholar 

  11. Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubule-associated protein tau is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci USA 83: 4044–4048

    Google Scholar 

  12. Kosik KS, Orecchio LD, Binder L, Trojanowski JQ, Lee VMY, Lee G (1988) Epitopes that span the tau molecule are shared with paired helical filaments. Neuron 1: 817–825

    Google Scholar 

  13. Ksiezak-Reding H, Wall JS (1994) Mass and physical dimensions of two distinet populations of paired helical filaments. Neurobiol Aging 15: 11–19

    Google Scholar 

  14. Ksiezak-Reding H, Yen S-H (1991) Structural stability of paired helical filaments requires microtubule-binding domains of tau: a model for self-association. Neuron 6: 717–728

    Google Scholar 

  15. Ksiezak-Reding H, Binder LI, Yen S-H (1990) Alzheimer disease proteins (A68) share epitopes with tau but show distinct biochemical properties. J Neurosci Res 25: 420–430

    Google Scholar 

  16. Ksiezak-Reding H, Lin W-K, Yen S-H (1992) Phosphate analysis and dephosphorylation of modified tau associated with paired helical filaments. Brain Res 597: 209–219

    Google Scholar 

  17. Lee VM-Y, Balin BJ, Otvos L Jr, Trojanowski JQ (1991) A68: a major subunit of paired helical filaments and derivatized forms of normal tau. Science 251: 675–678

    Google Scholar 

  18. Ohtsubo K, Izumiyama N, Shimada H, Tachikawa T, Nakamura H (1990) Three-dimensional structure of Alzheimer's neurofibrillary tangles of the aged human brain revealed by the quick-freeze, deep-etch replica method. Acta Neuropathol 79: 480–485

    Google Scholar 

  19. Pollanen MS, Markiewicz P, Bergeron C, Goh MC (1994) Twisted-ribbon structure of Alzheimer paired helical filaments revealed by atomic force microscopy. Am J Pathol 144: 869–873

    Google Scholar 

  20. Ruben GC, Iqbal K, Wisniewski HM, Johnson JE, Grundke-Iqbal I (1992) Alzheimer neurofibrillary tangles contain 2.1-nm filaments structurally identical to the microtubule-associated protein tau: a high resolution transmission electron microscope study of tangles and senile plaque core amyloid. Brain Res 590: 164–179

    Google Scholar 

  21. Ruben GC, Iqbal K, Grundke-Iqbal I, Johnson JE (1993) The organization of the microtubule-associated protein tau in Alzheimer paired helical filament. Brain Res 602: 1–13

    Google Scholar 

  22. Terry RD (1963) The fine structure of neurofibrillary tangles in Alzheimer's disease. J Neuropathol Exp Neurol 22: 629–642

    Google Scholar 

  23. Terry RD, Wisniewski HM (1970) The ultrastructure of the neurofibrillary tangle and the senile plaque. Alzheimer's disease and related conditions. Churchill, London, pp 143–165

    Google Scholar 

  24. Terry RD, Gonatas NK, Weiss M (1964) Ultrastructural studies in Alzheimer's presenile dementia. Am J Pathol 44: 269–297

    Google Scholar 

  25. Trojanowski JQ, Schmidt ML, Shin R-W, Bramblett GT, Rao D, Lee VM-Y (1993) Altered tau and neurofilament proteins in neurodegenerative diseases: diagnostic implications for Alzheimer's disease and Lewy body dementias. Brain Pathol 3: 45–54

    Google Scholar 

  26. Wen GY, Wisniewski HM (1987) High resolution analysis of paired helical filaments in Alzheimer's disease. J Electron Microsc Technol 5: 347–355

    Google Scholar 

  27. Wille H, Drewes G, Biernat J, Mandelkow EM, Mandelkow E (1992) Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J Cell Biol 118: 573–584

    Google Scholar 

  28. Wischik CM, Crowther RA, Stewart M, Roth M (1985) Subunit structure of paired helical filaments in Alzheimer's disease. J Cell Biol 100: 1905–1912

    Google Scholar 

  29. Wischik CM, Novak M, Thorgersen HC, 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 the paired helical filament of Alzheimer disease. Proc Natl Acad Sci USA 85: 4506–4510

    Google Scholar 

  30. Wischik CM, Novak M, Edwards PC, Klug A, Tichelaar W, Crowther RA (1988) Structural characterization of the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci USA 85: 4884–4888

    Google Scholar 

  31. Wisniewski HM, Wen GY (1985) Substructures of paired helical filaments from Alzheimer's disease neurofibrillary tangles. Acta Neuropathol (Berl) 66: 173–176

    Google Scholar 

  32. Wisniewski H, Terry RD, Hirano A (1970) Neurofibrillary pathology. J Neuropathol Exp Neurol 29: 163–176

    Google Scholar 

  33. Wisniewski HM, Narang HK, Terry RD (1976) Neurofibrillary tangles of paired helical filaments. J Neurol Sci 27: 173–181

    Google Scholar 

  34. Winsniewski HM, Merz PA, Iqbak K (1984) Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle. J Neuropathol Exp Neurol 43: 643–656

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pollanen, M.S., Markiewicz, P., Goh, M.C. et al. Alzheimer paired helical filaments: a comparison with the twisted ribbon model. Acta Neuropathol 90, 194–197 (1995). https://doi.org/10.1007/BF00294320

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00294320

Key words

Navigation