Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1987 Jun;127(3):559–568.

Filaments of Pick's bodies contain altered cytoskeletal elements.

G Perry, D Stewart, R Friedman, V Manetto, L Autilio-Gambetti, P Gambetti
PMCID: PMC1899769  PMID: 3296772

Abstract

Pick's disease, a form of progressive senile dementia, is distinguished by the presence of neuronal inclusions known as Pick's bodies. The Pick's body consists mostly of sparse 10-20-nm straight filaments admixed with other cytoplasmic elements. This ultrastructural study was undertaken to establish which components of the Pick's body share epitopes with the normal neuronal cytoskeleton and with Alzheimer's paired helical filaments. Vibratome sections from postmortem brains of patients afflicted with Pick's disease were immunostained by means of polyclonal and monoclonal antibodies to neurofilaments, an antiserum to microtubule proteins not cross-reacting with neurofilaments, and an antiserum to Alzheimer's paired helical filaments. All the antibodies have been shown previously to react with Alzheimer's paired helical filaments. The peroxidase-antiperoxidase or indirect immunogold procedure was used for immunostaining. In addition, we used Bodian's silver stain, which has a high affinity for neurofilaments. At the electron-microscopic level the antibodies and Bodian's silver reacted with the straight filaments and some amorphous elements contained within the Pick's body. The following preadsorptions blocked the immunoreaction: neurofilament antibodies with neurofilaments; microtubule antibodies with microtubule protein or a preparation of the microtubule associate protein, tau; antibodies to paired helical filaments with Alzheimer's brain tissue. Treatment of brain tissue containing Pick's bodies with sodium dodecyl sulfate, a solvent of the normal neuronal cytoskeleton, did not dissolve straight 12-nm filaments. The detergent extracted filaments contained the same isotopes as the Pick's filaments in intact tissue. These results demonstrate that the straight filament components of the Pick's body contain the same neurofilament and microtubule epitopes as the Alzheimer's paired helical filaments and that the filaments share insolubility characteristics similar to those of the paired helical filaments. It is proposed that these two structures are related and are derived at least in part from altered components of the normal neuronal cytoskeleton.

Full text

PDF
566

Images in this article

561Figure 1
on p.561
562Figure 2
on p.562
563Figure 3
on p.563
563Figure 4
on p.563
564Figure 5
on p.564
565Figure 6
on p.565
566Figure 7
on p.566

Selected References

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

  1. Aebi U., Cohn J., Buhle L., Gerace L. The nuclear lamina is a meshwork of intermediate-type filaments. Nature. 1986 Oct 9;323(6088):560–564. doi: 10.1038/323560a0. [DOI] [PubMed] [Google Scholar]
  2. Autilio-Gambetti L., Crane R., Gambetti P. Binding of Bodian's silver and monoclonal antibodies to defined regions of human neurofilament subunits: Bodian's silver reacts with a highly charged unique domain of neurofilaments. J Neurochem. 1986 Feb;46(2):366–370. doi: 10.1111/j.1471-4159.1986.tb12977.x. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Glenner G. G. Amyloid deposits and amyloidosis. The beta-fibrilloses (first of two parts). N Engl J Med. 1980 Jun 5;302(23):1283–1292. doi: 10.1056/NEJM198006053022305. [DOI] [PubMed] [Google Scholar]
  6. Glenner G. G. Amyloid deposits and amyloidosis: the beta-fibrilloses (second of two parts). N Engl J Med. 1980 Jun 12;302(24):1333–1343. doi: 10.1056/NEJM198006123022403. [DOI] [PubMed] [Google Scholar]
  7. Grundke-Iqbal I., Iqbal K., Quinlan M., Tung Y. C., Zaidi M. S., Wisniewski H. M. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem. 1986 May 5;261(13):6084–6089. [PubMed] [Google Scholar]
  8. 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]
  9. Kahn J., Anderton B. H., Gibb W. R., Lees A. J., Wells F. R., Marsden C. D. Neuronal filaments in Alzheimer's, Pick's, and Parkinson's diseases. N Engl J Med. 1985 Aug 22;313(8):520–521. doi: 10.1056/NEJM198508223130817. [DOI] [PubMed] [Google Scholar]
  10. Kosaka K., Oyanagi S., Matsushita M., Hori A. Presenile dementia with Alzheimer-, Pick- and Lewy-body changes. Acta Neuropathol. 1976 Nov 15;36(3):221–233. doi: 10.1007/BF00685366. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Lindwall G., Cole R. D. The purification of tau protein and the occurrence of two phosphorylation states of tau in brain. J Biol Chem. 1984 Oct 10;259(19):12241–12245. [PubMed] [Google Scholar]
  13. Metuzals J., Montpetit V., Clapin D. F. Organization of the neurofilamentous network. Cell Tissue Res. 1981;214(3):455–482. doi: 10.1007/BF00233488. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Perry G., Rizzuto N., Autilio-Gambetti L., Gambetti P. Paired helical filaments from Alzheimer disease patients contain cytoskeletal components. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3916–3920. doi: 10.1073/pnas.82.11.3916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Perry G., Selkoe D. J., Block B. R., Stewart D., Autilio-Gambetti L., Gambetti P. Electron microscopic localization of Alzheimer neurofibrillary tangle components recognized by an antiserum to paired helical filaments. J Neuropathol Exp Neurol. 1986 Mar;45(2):161–168. doi: 10.1097/00005072-198603000-00006. [DOI] [PubMed] [Google Scholar]
  17. Pogacar S., Rubio A. Morphological features of Pick's and atypical Alzheimer's disease in Down's syndrome. Acta Neuropathol. 1982;58(4):249–254. doi: 10.1007/BF00688605. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Rasool C. G., Selkoe D. J. Sharing of specific antigens by degenerating neurons in Pick's disease and Alzheimer's disease. N Engl J Med. 1985 Mar 14;312(11):700–705. doi: 10.1056/NEJM198503143121107. [DOI] [PubMed] [Google Scholar]
  20. Rewcastle N. B., Ball M. J. Electron microscopic structure of the "inclusion bodies" in Pick's disease. Neurology. 1968 Dec;18(12):1205–1213. doi: 10.1212/wnl.18.12.1205. [DOI] [PubMed] [Google Scholar]
  21. Schochet S. S., Jr, Lampert P. W., Lindenberg R. Fine structure of the Pick and Hirano bodies in a case of Pick's disease. Acta Neuropathol. 1968 Nov 1;11(4):330–337. doi: 10.1007/BF00686729. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Shibayama H., Kitoh J., Marui Y., Kobayashi H., Iwase S., Kayukawa Y. An unusual case of Pick's disease. Acta Neuropathol. 1983;59(2):79–87. doi: 10.1007/BF00691591. [DOI] [PubMed] [Google Scholar]
  24. Takauchi S., Hosomi M., Marasigan S., Sato M., Hayashi S., Miyoshi K. An ultrastructural study of Pick bodies. Acta Neuropathol. 1984;64(4):344–348. doi: 10.1007/BF00690400. [DOI] [PubMed] [Google Scholar]
  25. Towfighi J. Early Pick's disease. A light and ultrastructural study. Acta Neuropathol. 1972;21(3):224–231. doi: 10.1007/BF00688501. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. 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]
  29. Yoshimura N. Evidence that paired helical filaments originate from neurofilaments--electron microscope observations of neurites in senile plaques in the brain in Alzheimer's disease. Clin Neuropathol. 1984 Jan-Feb;3(1):22–27. [PubMed] [Google Scholar]

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

RESOURCES