Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1998 Jun;152(6):1531–1539.

Ferritin is associated with the aberrant tau filaments present in progressive supranuclear palsy.

M Pérez 1, J M Valpuesta 1, E M de Garcini 1, C Quintana 1, M Arrasate 1, J L López Carrascosa 1, A Rábano 1, J García de Yébenes 1, J Avila 1
PMCID: PMC1858430  PMID: 9626057

Abstract

Tau-containing filaments purified from the brain of progressive supranuclear palsy (PSP) patients were isolated and characterized. These filaments co-purify with regular particles that biophysical and biochemical methods identified as ferritin shells. In vivo, brain tau accumulation in PSP co-localized with ferritin. These results suggest that ferritin/iron could modulate the formation of tau aggregates in PSP.

Full text

PDF
1531

Images in this article

1533Figure 1
on p.1533
1534Figure 2
on p.1534
1534Figure 3
on p.1534
1535Figure 4
on p.1535
1536Figure 6
on p.1536

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arosio P., Levi S., Santambrogio P., Cozzi A., Luzzago A., Cesareni G., Albertini A. Structural and functional studies of human ferritin H and L chains. Curr Stud Hematol Blood Transfus. 1991;(58):127–131. doi: 10.1159/000419350. [DOI] [PubMed] [Google Scholar]
  2. Arrasate M., Pérez M., Valpuesta J. M., Avila J. Role of glycosaminoglycans in determining the helicity of paired helical filaments. Am J Pathol. 1997 Oct;151(4):1115–1122. [PMC free article] [PubMed] [Google Scholar]
  3. Auer I. A., Schmidt M. L., Lee V. M., Curry B., Suzuki K., Shin R. W., Pentchev P. G., Carstea E. D., Trojanowski J. Q. Paired helical filament tau (PHFtau) in Niemann-Pick type C disease is similar to PHFtau in Alzheimer's disease. Acta Neuropathol. 1995;90(6):547–551. doi: 10.1007/BF00318566. [DOI] [PubMed] [Google Scholar]
  4. Bancher C., Lassmann H., Budka H., Grundke-Iqbal I., Iqbal K., Wiche G., Seitelberger F., Wisniewski H. M. Neurofibrillary tangles in Alzheimer's disease and progressive supranuclear palsy: antigenic similarities and differences. Microtubule-associated protein tau antigenicity is prominent in all types of tangles. Acta Neuropathol. 1987;74(1):39–46. doi: 10.1007/BF00688336. [DOI] [PubMed] [Google Scholar]
  5. Bugiani O., Mancardi G. L., Brusa A., Ederli A. The fine structure of subcortical neurofibrillary tangles in progressive supranuclear palsy. Acta Neuropathol. 1979 Feb 15;45(2):147–152. doi: 10.1007/BF00691893. [DOI] [PubMed] [Google Scholar]
  6. Castellani R., Smith M. A., Richey P. L., Kalaria R., Gambetti P., Perry G. Evidence for oxidative stress in Pick disease and corticobasal degeneration. Brain Res. 1995 Oct 23;696(1-2):268–271. doi: 10.1016/0006-8993(95)00535-x. [DOI] [PubMed] [Google Scholar]
  7. Crowther R. A., Olesen O. F., Smith M. J., Jakes R., Goedert M. Assembly of Alzheimer-like filaments from full-length tau protein. FEBS Lett. 1994 Jan 10;337(2):135–138. doi: 10.1016/0014-5793(94)80260-2. [DOI] [PubMed] [Google Scholar]
  8. Dexter D. T., Carayon A., Javoy-Agid F., Agid Y., Wells F. R., Daniel S. E., Lees A. J., Jenner P., Marsden C. D. Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia. Brain. 1991 Aug;114(Pt 4):1953–1975. doi: 10.1093/brain/114.4.1953. [DOI] [PubMed] [Google Scholar]
  9. Flament S., Delacourte A., Verny M., Hauw J. J., Javoy-Agid F. Abnormal Tau proteins in progressive supranuclear palsy. Similarities and differences with the neurofibrillary degeneration of the Alzheimer type. Acta Neuropathol. 1991;81(6):591–596. doi: 10.1007/BF00296367. [DOI] [PubMed] [Google Scholar]
  10. Focht S. J., Snyder B. S., Beard J. L., Van Gelder W., Williams L. R., Connor J. R. Regional distribution of iron, transferrin, ferritin, and oxidatively-modified proteins in young and aged Fischer 344 rat brains. Neuroscience. 1997 Jul;79(1):255–261. doi: 10.1016/s0306-4522(96)00607-0. [DOI] [PubMed] [Google Scholar]
  11. García de Ancos J., Correas I., Avila J. Differences in microtubule binding and self-association abilities of bovine brain tau isoforms. J Biol Chem. 1993 Apr 15;268(11):7976–7982. [PubMed] [Google Scholar]
  12. Ghatak N. R., Nochlin D., Hadfield M. G. Neurofibrillary pathology in progressive supranuclear palsy. Acta Neuropathol. 1980;52(1):73–76. doi: 10.1007/BF00687231. [DOI] [PubMed] [Google Scholar]
  13. Goedert M., Jakes R., Spillantini M. G., Hasegawa M., Smith M. J., Crowther R. A. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature. 1996 Oct 10;383(6600):550–553. doi: 10.1038/383550a0. [DOI] [PubMed] [Google Scholar]
  14. Goedert M., Spillantini M. G., Jakes R., Rutherford D., Crowther R. A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. Neuron. 1989 Oct;3(4):519–526. doi: 10.1016/0896-6273(89)90210-9. [DOI] [PubMed] [Google Scholar]
  15. Greenberg S. G., Davies P. A preparation of Alzheimer paired helical filaments that displays distinct tau proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5827–5831. doi: 10.1073/pnas.87.15.5827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Grundke-Iqbal I., Fleming J., Tung Y. C., Lassmann H., Iqbal K., Joshi J. G. Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia. Acta Neuropathol. 1990;81(2):105–110. doi: 10.1007/BF00334497. [DOI] [PubMed] [Google Scholar]
  17. Grundke-Iqbal I., Iqbal K., Tung Y. C., Quinlan M., Wisniewski H. M., Binder L. I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4913–4917. doi: 10.1073/pnas.83.13.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hirokawa N., Shiomura Y., Okabe S. Tau proteins: the molecular structure and mode of binding on microtubules. J Cell Biol. 1988 Oct;107(4):1449–1459. doi: 10.1083/jcb.107.4.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Iwatsubo T., Hasegawa M., Ihara Y. Neuronal and glial tau-positive inclusions in diverse neurologic diseases share common phosphorylation characteristics. Acta Neuropathol. 1994;88(2):129–136. doi: 10.1007/BF00294505. [DOI] [PubMed] [Google Scholar]
  22. Jellinger K., Riederer P., Tomonaga M. Progressive supranuclear palsy: clinico-pathological and biochemical studies. J Neural Transm Suppl. 1980;(16):111–128. doi: 10.1007/978-3-7091-8582-7_12. [DOI] [PubMed] [Google Scholar]
  23. Kosik K. S., Joachim C. L., Selkoe D. J. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4044–4048. doi: 10.1073/pnas.83.11.4044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ksiezak-Reding H., Morgan K., Mattiace L. A., Davies P., Liu W. K., Yen S. H., Weidenheim K., Dickson D. W. Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. Am J Pathol. 1994 Dec;145(6):1496–1508. [PMC free article] [PubMed] [Google Scholar]
  25. Ksiezak-Reding H., Yen S. H. Structural stability of paired helical filaments requires microtubule-binding domains of tau: a model for self-association. Neuron. 1991 May;6(5):717–728. doi: 10.1016/0896-6273(91)90169-z. [DOI] [PubMed] [Google Scholar]
  26. Ledesma M. D., Bonay P., Colaço C., Avila J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem. 1994 Aug 26;269(34):21614–21619. [PubMed] [Google Scholar]
  27. Medina M., Montejo de Garcini E., Avila J. The role of tau phosphorylation in transfected COS-1 cells. Mol Cell Biochem. 1995 Jul 5;148(1):79–88. doi: 10.1007/BF00929506. [DOI] [PubMed] [Google Scholar]
  28. Montejo de Garcini E., Carrascosa J. L., Correas I., Nieto A., Avila J. Tau factor polymers are similar to paired helical filaments of Alzheimer's disease. FEBS Lett. 1988 Aug 15;236(1):150–154. doi: 10.1016/0014-5793(88)80304-1. [DOI] [PubMed] [Google Scholar]
  29. Moreno F. J., Medina M., Pérez M., Montejo de Garcini E., Avila J. Glycogen synthase kinase 3 phosphorylates recombinant human tau protein at serine-262 in the presence of heparin (or tubulin). FEBS Lett. 1995 Sep 18;372(1):65–68. doi: 10.1016/0014-5793(95)00934-2. [DOI] [PubMed] [Google Scholar]
  30. Nieto A., Correas I., Montejo de Garcini E., Avila J. A modified form of microtubule-associated tau protein is the main component of paired helical filaments. Biochem Biophys Res Commun. 1988 Jul 29;154(2):660–667. doi: 10.1016/0006-291x(88)90190-8. [DOI] [PubMed] [Google Scholar]
  31. Nishimura T., Ikeda K., Akiyama H., Kondo H., Kato M., Li F., Iseki E., Kosaka K. Immunohistochemical investigation of tau-positive structures in the cerebral cortex of patients with progressive supranuclear palsy. Neurosci Lett. 1995 Dec 8;201(2):123–126. doi: 10.1016/0304-3940(95)12151-x. [DOI] [PubMed] [Google Scholar]
  32. Powell H. C., London G. W., Lampert P. W. Neurofibrillary tangles in progressive supranuclear palsy. Electron microscopic observations. J Neuropathol Exp Neurol. 1974 Jan;33(1):98–106. doi: 10.1097/00005072-197401000-00007. [DOI] [PubMed] [Google Scholar]
  33. Pérez M., Valpuesta J. M., Medina M., Montejo de Garcini E., Avila J. Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau-tau interaction. J Neurochem. 1996 Sep;67(3):1183–1190. doi: 10.1046/j.1471-4159.1996.67031183.x. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Rubenstein R., Kascsak R. J., Merz P. A., Wisniewski H. M., Carp R. I., Iqbal K. Paired helical filaments associated with Alzheimer disease are readily soluble structures. Brain Res. 1986 Apr 30;372(1):80–88. doi: 10.1016/0006-8993(86)91460-5. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Schmidt M. L., Huang R., Martin J. A., Henley J., Mawal-Dewan M., Hurtig H. I., Lee V. M., Trojanowski J. Q. Neurofibrillary tangles in progressive supranuclear palsy contain the same tau epitopes identified in Alzheimer's disease PHFtau. J Neuropathol Exp Neurol. 1996 May;55(5):534–539. doi: 10.1097/00005072-199605000-00006. [DOI] [PubMed] [Google Scholar]
  38. Schweers O., Mandelkow E. M., Biernat J., Mandelkow E. Oxidation of cysteine-322 in the repeat domain of microtubule-associated protein tau controls the in vitro assembly of paired helical filaments. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8463–8467. doi: 10.1073/pnas.92.18.8463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schweers O., Schönbrunn-Hanebeck E., Marx A., Mandelkow E. Structural studies of tau protein and Alzheimer paired helical filaments show no evidence for beta-structure. J Biol Chem. 1994 Sep 30;269(39):24290–24297. [PubMed] [Google Scholar]
  40. Scott C. W., Fieles A., Sygowski L. A., Caputo C. B. Aggregation of tau protein by aluminum. Brain Res. 1993 Nov 19;628(1-2):77–84. doi: 10.1016/0006-8993(93)90940-o. [DOI] [PubMed] [Google Scholar]
  41. Shu S. Y., Ju G., Fan L. Z. The glucose oxidase-DAB-nickel method in peroxidase histochemistry of the nervous system. Neurosci Lett. 1988 Feb 29;85(2):169–171. doi: 10.1016/0304-3940(88)90346-1. [DOI] [PubMed] [Google Scholar]
  42. Smith M. A., Harris P. L., Sayre L. M., Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9866–9868. doi: 10.1073/pnas.94.18.9866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Smith M. A., Kutty R. K., Richey P. L., Yan S. D., Stern D., Chader G. J., Wiggert B., Petersen R. B., Perry G. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. Am J Pathol. 1994 Jul;145(1):42–47. [PMC free article] [PubMed] [Google Scholar]
  44. Smith M. A., Perry G. Free radical damage, iron, and Alzheimer's disease. J Neurol Sci. 1995 Dec;134 (Suppl):92–94. doi: 10.1016/0022-510x(95)00213-l. [DOI] [PubMed] [Google Scholar]
  45. Smith M. A., Perry G., Richey P. L., Sayre L. M., Anderson V. E., Beal M. F., Kowall N. Oxidative damage in Alzheimer's. Nature. 1996 Jul 11;382(6587):120–121. doi: 10.1038/382120b0. [DOI] [PubMed] [Google Scholar]
  46. Smith M. A., Sayre L. M., Monnier V. M., Perry G. Oxidative posttranslational modifications in Alzheimer disease. A possible pathogenic role in the formation of senile plaques and neurofibrillary tangles. Mol Chem Neuropathol. 1996 May-Aug;28(1-3):41–48. doi: 10.1007/BF02815203. [DOI] [PubMed] [Google Scholar]
  47. Spillantini M. G., Crowther R. A., Goedert M. Comparison of the neurofibrillary pathology in Alzheimer's disease and familial presenile dementia with tangles. Acta Neuropathol. 1996 Jul;92(1):42–48. doi: 10.1007/s004010050487. [DOI] [PubMed] [Google Scholar]
  48. Stadtman E. R. Protein oxidation and aging. Science. 1992 Aug 28;257(5074):1220–1224. doi: 10.1126/science.1355616. [DOI] [PubMed] [Google Scholar]
  49. Tabaton M., Whitehouse P. J., Perry G., Davies P., Autilio-Gambetti L., Gambetti P. Alz 50 recognizes abnormal filaments in Alzheimer's disease and progressive supranuclear palsy. Ann Neurol. 1988 Sep;24(3):407–413. doi: 10.1002/ana.410240309. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. 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]
  52. Theil E. C. Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms. Annu Rev Biochem. 1987;56:289–315. doi: 10.1146/annurev.bi.56.070187.001445. [DOI] [PubMed] [Google Scholar]
  53. Tomonaga M. Ultrastructure of neurofibrillary tangles in progressive supranuclear palsy. Acta Neuropathol. 1977 Feb 28;37(2):177–181. doi: 10.1007/BF00692065. [DOI] [PubMed] [Google Scholar]
  54. Troncoso J. C., Costello A., Watson A. L., Jr, Johnson G. V. In vitro polymerization of oxidized tau into filaments. Brain Res. 1993 Jun 11;613(2):313–316. doi: 10.1016/0006-8993(93)90918-d. [DOI] [PubMed] [Google Scholar]
  55. Wille H., Drewes G., Biernat J., Mandelkow E. M., Mandelkow E. Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J Cell Biol. 1992 Aug;118(3):573–584. doi: 10.1083/jcb.118.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wischik C. M., Novak M., Thøgersen H. C., Edwards P. C., Runswick M. J., Jakes R., Walker J. E., Milstein C., Roth M., Klug A. Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4506–4510. doi: 10.1073/pnas.85.12.4506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wood J. G., Mirra S. S., Pollock N. J., Binder L. I. Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau) Proc Natl Acad Sci U S A. 1986 Jun;83(11):4040–4043. doi: 10.1073/pnas.83.11.4040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. 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]
  59. Yan S. D., Chen X., Schmidt A. M., Brett J., Godman G., Zou Y. S., Scott C. W., Caputo C., Frappier T., Smith M. A. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7787–7791. doi: 10.1073/pnas.91.16.7787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. 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]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES