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Vulnerability of the Neuronal Cytoskeleton in Aging and Alzheimer Disease: Widespread Involvement of All Three Major Filament Systems

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Special Focus on the Biology of Aging

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Abstract

Alzheimer disease (AD) is the commonest cause of dementia in the elderly (for recent reviews, see Chiu, 1989; Henderson & Finch, 1989; Katzman et al., 1988). As a consequence of the increasing number of people living beyond the seventh decade, AD has become the fourth leading cause of death in the United States. Despite the recognition of AD and the brain pathology associated with it more than 80 years ago (Alzheimer, 1907), the pathogenesis and etiology of AD remain enigmatic. Several reasons account for this such as (1) the complexity and limited understanding of the central nervous system (CNS); (2) an incomplete definition of AD and variants thereof; (3) the lack of animal models for hypothesis testing; (4) overlap between early AD and normal aging as well as between AD and other neurodegenerative diseases. For example, patients with idiopathic Parkinson disease (PD) frequently develop cognitive impairments, AD patients often exhibit extrapyramidal signs, and diminished olfaction is observed in AD and PD subjects (Chiu, 1989; Doty et al., 1987, 1989).

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References

  • Alzheimer, A. (1907). Ueber eine eigenartige erkrankung der hirnrinde. Allgemeine Zeitschrift für Psychiatrie, 64, 146–148.

    Google Scholar 

  • Anderton, B. H., Breinburg, D., Downes, M. J., Green, P. J., Tomlinson, B. E., Ulrich, J., Wood, J. N., & Kahn, J. (1982). Monoclonal antibodies show that neurofibrillary tangles and neurofilaments share antigenic determinants. Nature, 298, 84–86.

    Article  PubMed  CAS  Google Scholar 

  • Arai, H., Lee, V. M. Y., Otvos, L. Jr., Greenberg, B. D., Lowery, D. E., Sharma, S., Schmidt, M. L., & Trojanowski, J. Q. (1990). Defined neurofilament, Ï„ and β -amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques. Proceedings of the National Academy of Sciences, USA, 87, 2249–2253.

    Article  CAS  Google Scholar 

  • Bancher, C., Lassman, H., Budka, H., Jellinger, K., Grundke-Iqball, I., Iqbal, K., Wiche, G., Seitelberger, F., & Wisniewski, H. M. (1989). An antigenic profile of Lewy bodies: Immunocytochemical indication for protein phosphorylation and ubiquitination. Journal of Neuropathology & Experimental Neurology, 48, 81–93.

    Article  CAS  Google Scholar 

  • Braak, H., & Braak, E. (1988). Neuropil threads occur in dendrites of tangle-bearing nerve cells. Neuropathology & Applied Neurobiology, 14, 39–44.

    Article  CAS  Google Scholar 

  • Braak, H., Braak, E., Grundke-Iqbal, I., & Iqbal, K. (1986). Occurrence of neuropil threads in the senile human brain and in Alzheimer’s disease: A third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neuroscience Letters, 65, 351–355.

    Article  PubMed  CAS  Google Scholar 

  • Brion, J. P., Passarier, H., Nunez, J., & Flament-Durand, J. (1985). Immunologic determinants of tau protein are present in neurfibrillary tangles of Alzheimer’s disease. Archives of Biology, 95, 229–235.

    Google Scholar 

  • Chui, H. C. (1989). Dementia: A review emphasizing clinicopathologic correlation and brain-behavior relationships. Archives of Neurology, 46, 806–814.

    Article  PubMed  CAS  Google Scholar 

  • Dahl, D., Selkoe, D. J., Pero, R. T., Bignami, A. (1982). Immunostaining of neurofibrillary tangles in Alzheimer’s senile dementia with a neurofilament antiserum. Journal of Neuroscience, 2, 113–119.

    PubMed  CAS  Google Scholar 

  • Davis, R. L., & Robertson, D. M. (1985). A textbook of neuropathology. Baltimore: Williams & Wilkins.

    Google Scholar 

  • Dickson, D. W., Crystal, H., Mattiace, L. A., Kress, Y., Schwagerl, A., Ksiezak-Reding, H., Davies, P., & Yen, S. H. (1989). Diffuse lewy body disease: Light and electron microscopic immunocytochemistry of senile plaques. Acta Neuropathologica, 78, 572–584.

    Article  PubMed  CAS  Google Scholar 

  • Dickson, D. W., Davies, P., Mayeux, R., Crystal, H., Horoupian, D. S., Thompson, A., & Goldman, J. E. (1987). Diffuse lewy body disease. Acta Neuropathologica, 75, 8–15.

    Article  PubMed  CAS  Google Scholar 

  • Dickson, D. W., Ksiezak-Reding, H., Crowe, A., & Yen, S. H. (1987). Monoclonal antibodies show cross reactivity of Alzheimer neurofibrillary tangles and heat-stable microtubule associated proteins. In G. Perry (Ed.), Alterations in the neuronal cytoskeleton in Alzheimer disease, (pp. 165–167). New York: Plenum.

    Chapter  Google Scholar 

  • Doty, R. L., Riklan, M., Deems, D. A., Reynolds, C., & Stellar, S. (1989). The olfactory and cognitive deficits of Parkinson’s disease: Evidence for independence. Annuals of Neurology, 25, 166–171.

    Article  CAS  Google Scholar 

  • Doty, R. L., Reyes, P. F., & Gregor, T. (1987). Presence of both odor identification and detection deficits in Alzheimer’s disease. Brain Research Bulletin, 18, 597–600.

    Article  PubMed  CAS  Google Scholar 

  • Gambetti, P., Autilio-Gambetti, L., Perry, G., Shecket, G., & Crane, R. C. (1983). Antibodies to neurofibrillary tangles of Alzheimer’s disease raised from human and animal neurofilament fractions. Laboratory Investigation, 49, 430–435.

    PubMed  CAS  Google Scholar 

  • Galloway, P., Bergeron, C., & Perry, G. (1989). The presence of tau distinguishes Lewy bodies of diffuse Lewy body from those of idiopathic Parkinson disease. Neuroscience Letters, 100, 6–10.

    Article  PubMed  CAS  Google Scholar 

  • Galloway, P. G., Grundke-Ibal, I., Iqbal, K., & Perry, G. (1988). Lewy bodies contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. Journal of Neuropathology & Experimental Neurology, 47, 654–663.

    Article  CAS  Google Scholar 

  • Galloway, P., & Perry, G. (1987). Microfilament involvement in Hirano body formation. In G. Perry (Ed.), Alterations in the neuronal cytoskeleton in Alzheimer disease (pp. 199–210). New York: Plenum.

    Chapter  Google Scholar 

  • Galloway, P. G., Perry, G., & Gambetti, P. (1987). Hirano body filaments contain actin and actin-associated proteins. Journal of Neuropathology &. Experimental Neurology, 46, 262–268.

    Article  Google Scholar 

  • Galloway, P. G., Perry, G., Kosik, K. S., & Gambetti, P. (1987). Hirano bodies contain tau protein. Brain Research, 403, 337–340.

    Article  PubMed  CAS  Google Scholar 

  • Gibb, W. R. G., & Lees, A. J. (1989). The significance of the Lew body in the diagnosis of idiopathic Parkinson’s disease. Neuropathology & Applied Neurobiology, 15, 27 – 44.

    Article  CAS  Google Scholar 

  • Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., & Klug, A. (1988). Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau. Proceedings of the National Academy of Sciences USA, 85, 4051–4055.

    Article  CAS  Google Scholar 

  • Goldman, J. E. (1983). The association of actin with Hirano bodies. Journal of Neuropathology & Experimental Neurology, 42, 146–152.

    Article  CAS  Google Scholar 

  • Goldman, J. E. (1987). Cytoskeletal abnormalities in Parkinson’s disease. In G. Perry (Ed.), Alterations in the neuronal cytoskeleton in Alzheimer disease (pp. 191–197). New York: Plenum.

    Chapter  Google Scholar 

  • Goldman, J. E., Yen, S. H., Chiu, F. C., & Peress, N. S. (1983). Lewy bodies of Parkinson’s disease contain neurofilament antigens. Science, 221, 1082–1084.

    Article  PubMed  CAS  Google Scholar 

  • Grunde-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1987). Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences, USA, 83, 4913–4917.

    Article  Google Scholar 

  • Henderson, V. W., & Finch, C. E. (1989). The neurobiology of Alzheimer’s disease. Journal of Neurosurgery, 70, 335–353.

    Article  PubMed  CAS  Google Scholar 

  • Hill, W. D., Lee, V. M. Y., Hurtig, H. I., Murray, J. M., & Trojanowski, J. Q. (1990). Lewy body neurofilament epitope analysis and localization. Manuscript submitted for publication.

    Google Scholar 

  • Ihara, Y. (1988). Massive somatodendritic sprouting of cortical neurons in Alzheimer’s disease. Brain Research, 459, 138–144.

    Article  PubMed  CAS  Google Scholar 

  • Katzman, R., Lasker, B., & Bernstein, N. (1988). Advances in the diagnosis of dementia: Accuracy of diagnosis and consequences of misdiagnosis of disorders causing dementia. In R. D. Terry (Ed.), Aging and the brain (pp. 17–62). New York: Raven Press.

    Google Scholar 

  • Kosik, K., Joachim, C. L., & Selkoe, D. J. (1986). Microtubule-associated protein tau is a major antigenic component of paired helical filaments in Alzheimer’s disease. Proceedings of the National Academy of Sciences, USA, 83, 4044–4048.

    Article  CAS  Google Scholar 

  • Kosik, K. S., Orrechio, L. D., Binder, L., Trojanowski, J. Q., Lee, V. M. Y., & Lee, G. (1988). Epitopes that nearly span the tau molecule are shared with paired helical filaments. Neuron, 1, 817–825.

    Article  PubMed  CAS  Google Scholar 

  • Ksiezak-Reding, H., Dickson, D. W., Davies, P., & Yen, S. H. (1987). Recognition of tau epitopes by anti-neurofilament antibodies that bind to Alzheimer neurofibrillary tangles. Proceedings of the National Academy of Sciences, USA, 84, 3410–3414.

    Article  CAS  Google Scholar 

  • Lee, V. M. Y., Otvos, L., Cardin, M. J., Hollosi, M., Dietzschold, B., & Lazzarini, R. A. (1988a). Identification of the major multi-phosphorylation site in mammalian neurofilaments. Proceedings of the National Academy of Sciences, USA, 85, 1998 – 2002.

    Article  CAS  Google Scholar 

  • Lee, V. M. Y., Otvos, L. Jr., Schmidt, M. L., & Trojanowski, J. Q. (1988b). Alzheimer’s neurofibrillary tangles share immunological homologies with multi-phosphorylation domains in the two large neurofilament proteins. Proceedings of the National Academy of Sciences, USA, 85, 7384–7388.

    Article  CAS  Google Scholar 

  • Lennox, G., Lowe, J., Landon, M., Byrne, E., Mayer, R. J., & Godwin-Austen, R. B. (1989). Diffuse Lewy body disease: Correlative neuropathology using anti-ubiquitin immunocytochemistry. Journal of Neurology, Neurosurgery & Psychiatry, 52, 1236 – 1247.

    Article  CAS  Google Scholar 

  • Love, S., Saitoh, T., Quijada, S., Cole, G. M., & Terry, R. D. (1988). Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, Pick bodies and Lewy bodies. Journal of Neuropathology & Experimental Neurology, 47, 393–405.

    Article  CAS  Google Scholar 

  • Miller, C., Brion, J. P., Calvert, R., Chin, T. L., Eagles, P. A. M., Downes, M. J., Flament-Durand, J., Haugh, M., Kahn, J., Probst, A., Ulrich, J., & Anderton, B. H. (1986). Alzheimer paired helical filaments share epitopes with neurofilament sidearms. EMBO Journal, 5, 269–276.

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nakazato, Y., Sasaki, A., Hirato, J., & Ishida, Y. (1984). Immunohistochemical localization of neurofilament protein neuronal degenerations. Acta Neuropathologica, 64, 30–36.

    Article  PubMed  CAS  Google Scholar 

  • Nukina, N., Kosik, K. S., & Selkoe, D. J. (1987). Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies due to cross reaction with tau protein. Proceedings of the National Academy of Sciences, USA, 84, 3415–3419.

    Article  CAS  Google Scholar 

  • Otvos, L., Lee, V. M. Y., Hollosi, M., Perczel, A., & Dietzschold, B. (1988).Phosphorylation of synthetic mid-sized neurofilament protein fragment changes the secondary structure and antibody recognition of this peptide. In T. Shiba & S. Sakakibara (Eds.), Peptide Chemistry (pp. 799–802). Osaka: Protein Research Foundation.

    Google Scholar 

  • Pappolla, M. A. (1986). Lewy bodies of Parkinson’s disease. Archives of Pathology & Laboratory Medicine, 110, 1160–1163.

    CAS  Google Scholar 

  • Perry, G., Mulvihill, P., Manetto, V., Autilio-Gambetti, L., & Gambetti, P. (1987). Immunocytochemical properties of Alzheimer straight filaments. Journal of Neuroscience, 7, 3736–3738.

    PubMed  CAS  Google Scholar 

  • Perry, G., Rizzuto, N., Autilio-Gambetti, L., & Gambetti, P. (1985). Paired helical filaments from Alzheimer disease patients contain cytoskeletal components. Proceedings of the National Academy of Sciences, USA, 82, 3916–3920.

    Article  CAS  Google Scholar 

  • Price, D. L., Koo, E. H., & Unterbeck, A. (1989). Cellular and molecular biology of Alzheimer’s disease. BioEssays, 10, 69–14.

    Article  PubMed  CAS  Google Scholar 

  • Probst, A., Ulrich, J., & Heitz, P. H. U. (1982). Senile dementia of Alzheimer type: Astroglial reaction to extracellular neurofibrillary tangles in the hippocampus: An immunohistochemical and electron-microscopic study. Acta Neuropathologica, 57, 75–79.

    Article  PubMed  CAS  Google Scholar 

  • Roher, A. E., Palmer, K. C, Chau, V., & Ball, M. J. (1988). Isolation and chemical characterization of Alzheimer’s disease paired helical filament cytoskeletons: Differentiation from amyloid plaque core protein. Journal of Cell Biology, 107, 2703–2716.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, M. L., Gur, R., Gur, R. C., & Trojanowski, J. Q. (1988). Intraneuronal and extracellular neurofibrillary tangles exhibit mutually exclusive cytoskeletal antigen. Annals of Neurology, 23, 184–189.

    Article  PubMed  CAS  Google Scholar 

  • Schmidt, M. L., Lee, V. M. Y., Hurtig, H., & Trojanowski, J. Q. (1988). Properties of antigenic determinants that distinguish neurofibrillary tangles in progressive supranuclear palsy and Alzheimer’s disease. Laboratory Investigation, 59, 460–466.

    PubMed  CAS  Google Scholar 

  • Schmidt, M. L., Lee, V. M. Y., & Trojanowski, J. Q. (1989). Analysis of epitopes shared by Hirano bodies and human neurofilament proteins in normal and Alzheimer’s disease hippocampus. Laboratory Investigation, 60, 513–522.

    PubMed  CAS  Google Scholar 

  • Schmidt, M. L., Lee, V. M. Y., & Trojanowski, J. Q. (1990a). Relative abundance of tau and neurofilament epitopes in hippocampal neurofibrillary tangles. American Journal of Pathology.

    Google Scholar 

  • Schmidt, M. L., Lee, V. M. Y., & Trojanowski, J. Q. (1990b). Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer’s disease senile plaque neuntes and neuropil threads. Laboratory Investigation, in press.

    Google Scholar 

  • Selkoe, D. J. (1989). Biochemistry of altered brain proteins in Alzheimer’s disease. Annual Revue of Neuroscience, 12, 463–490.

    Article  CAS  Google Scholar 

  • Sternberger, N. H., Sternberger, L. A., & Ulrich, J. (1985). Aberrant neurofilament phosphorylation in Alzheimer’s disease. Proceedings of the National Academy of Sciences, USA, 82, 4274–4276.

    Article  CAS  Google Scholar 

  • Talamo, B. R., Rudell, R., Kosik, K. S., Lee, V. M. Y., Neff, S., Adelman, L., & Kauer, J. S. (1989). Pathological changes in olfactory neurons in patients with Alzheimer’s disease. Nature, 337, 736–739.

    Article  PubMed  CAS  Google Scholar 

  • Wischik, C.M., Novak, M., Thorgersen, H. C., Edwards, P. C., Runs wick, M. J., Rakes, R., Walker, J., 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. Proceedings of the National Academy of Sciences, USA, 85, 4506–4510.

    Article  CAS  Google Scholar 

  • Wood, J. G., Mirra, S. S., Pollock, N. J., & Binder, L. I. (1986). Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau. Proceedings of the National Academy of Sciences, USA, 83, 4040–4043.

    Article  CAS  Google Scholar 

  • Yen, S. H., Dickson, D. W., Crowe, A., Butler, M., & Shelanski, M. L. (1987). Alzheimer’s neurofibrillary tangles contain unique epitopes and epitopes in common with the heat-stable microtubule associated proteins tau and MAP2. American Journal of Pathology, 126, 81–91.

    PubMed  CAS  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. University of Pennsylvania School of Medicine and Wistar Institute, USA

    J. Q. Trojanowski, M. L. Schmidt, L. Otvos Jr., H. Arai, W. D. Hill & V. M.-Y. Lee

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  1. J. Q. Trojanowski
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  2. M. L. Schmidt
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  3. L. Otvos Jr.
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  4. H. Arai
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  6. V. M.-Y. Lee
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Editors and Affiliations

  1. Center for Gerontological Research, Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia, PA, USA

    Vincent J. Cristofalo Ph.D.

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Trojanowski, J.Q., Schmidt, M.L., Otvos, L., Arai, H., Hill, W.D., Lee, V.MY. (1991). Vulnerability of the Neuronal Cytoskeleton in Aging and Alzheimer Disease: Widespread Involvement of All Three Major Filament Systems. In: Cristofalo, V.J., Lawton, M.P. (eds) Special Focus on the Biology of Aging. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-38445-9_10

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  • DOI: https://doi.org/10.1007/978-3-662-38445-9_10

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