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Amyloidosis pp 703-708 | Cite as

Neurobiological Probes for Specific Constituents of Senile Plaques in Aging and Alzheimer’s Disease

  • Donald L. Price
  • Robert G. Struble
  • Cheryl A. Kitt
  • Linda C. Cork
  • Lary C. Walker
  • Manuel F. Casanova
  • Richard E. Powers

Abstract

Senile plaques are composed of neurites (enlarged axons, nerve terminals, and, possibly, dendrites) associated with focal deposits of amyloid. Plaques are present in small numbers in the amygdala, hippocampus, and neocortex in elderly primates and are abundant in these regions in individuals with Alzheimer’s disease. Aged macaques provide a model for investigations of plaques. One of the earliest abnormalities identified in these older animals is multifocal enlargement of individual axons within the cortex. Later, enlarged neurites appear in clusters (neurite plaques); in mixed plaques, neurites are associated with amyloid. In the oldest animals, many plaques show relatively greater proportions of amyloid. These observations are interpreted to indicate that axonal pathology is an early event and that plaques evolve from the neurite type to the amyloid type. Using antibody probes, we have identified abnormal axons and neurites derived from cholinergic, monoaminergic, and peptidergic systems. These axons and neurites also show accumulations of cytoskeletal antigens, including neurofilament peptides. Similarly, in human tissues, these approaches have identified abnormalities of the cytoskeleton and demonstrated a variety of transmitter-specific antigens in plaques.

Keywords

Basal Forebrain Senile Plaque Axonal Pathology Mixed Plaque Substantia Innominata 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References and Notes

  1. 1.
    R. T. Bartus, R. L. Dean III, B. Beer, and A. S. Lippa, Science, 217: 408–417 (1982); R. T. Davis, Exp. Gerontol., 13:237–250 (1978); S. K. Presty et al., Soc. Neurosci. Abstr., 10:774 (1984); D. L. Price et al., in: Behavior and Pathology of Aging in Rhesus Monkeys, R. T. Davis and C. W. Leathers, Eds. (Alan R. Liss, New York, in press).CrossRefGoogle Scholar
  2. 2.
    D. L. Price et al., in: Behavior and Pathology of Aging in Rhesus Monkeys, R. T. Davis and C. W. Leathers, Eds. (Alan R. Liss, New York, in press); R. G. Struble, L. C. Cork, P. J. Whitehouse and D. L. Price, Science, 216:413–415 (1982); R. G. Struble, J. C. Hedreen, L. C. Cord, and D. L. Price, Neurobiol. Aging (in press); R. G. Struble, D. L. Price Jr., L. C. Cork, and D. L. Price, Senile plaques in the neocortex of aged monkeys (submitted for publication); H. M. Wisniewski, B. Ghetti and R. D. Terry, J. Neuropathol. Exp. Neurol., 32:566–584 (1973).Google Scholar
  3. 3.
    G. Blessed, B. E. Tomlinson, and M. Roth, Br. J. Psychiatry, 114: 797–811 (1968); B. E. Tomlinson, G. Blessed, and M. Roth, J. Neurol. Sci., 11: 205–242 (1970).CrossRefGoogle Scholar
  4. 4.
    C. A. Kitt et al., Science (in press); C. A. Kitt et al., Catechol- aminergic neurites in senile plaques in prefrontal cortex of aged nonhuman primates (submitted for publication); R. G. Struble, J. C. Hedreen, L. C. Cord, and D. L. Price, Neurobiol. Aging (in press); 5. R. G. Struble, C. A. Kitt, L. C. Walker, L. C. Cord, and D. L. Price, Brain Pres. (in press).Google Scholar
  5. 5.
    R. G. Struble, L. C. Cork, P. J. Whitehouse, and D. L. Price, Science, 216:413–415 (1982); R. G. Struble, J. C. Hedren, L. C. Cordk, and D. L. Price, Neurobiol. Aging (in press).CrossRefGoogle Scholar
  6. 6.
    H. M. Wisniewski and R. D. Terry RD, in: Progress in Neuropathology, H. M. Zimmerman, Ed. ( Grune and Stratton, New York, 1973 ), Vol. II, pp. 1–26.Google Scholar
  7. 7.
    B. H. Anderton et al., Nature, 298:84–86 (1982); L. Autilio-Gambetti, P. Gambetti, and R. C. Crane, Banbury Rep., 15:117–124 (1983); P. Gambetti, G. Shecket, B. Shetti, A. Hirano, and D. Dahl, J. Neuropathol. Exp. Neurol., 42:69–79 (1983); D. J. Selkoe, Y. Ihara, and F. J. Salazar, Science, 215:1243–1245 (1982); G. P. Wang, I. Grundke- Iqbal, R. J. Kascsak, K. Iqbal, and H. M. Wisneiwski, Acta Neuropathol., 62: 268–275 (1984).Google Scholar
  8. 8.
    N. Nukina and Y. Ihara, Proc. Jpn. Acad., 59: 284–287 (1983).CrossRefGoogle Scholar
  9. 9.
    N. Nukina and Y. Ihara, Proc. Jpn. Acad., 59: 288–292 (1983).CrossRefGoogle Scholar
  10. 10.
    J. M. Powers, W. W. Schlaepfer, M. C. Willingham, and B. J. Hall, J. Neuropathol. Exp. Neurol., 40:592–612 (1981); D. L. Price et al., Neurosci. Comment., 1, 84–92 (1982).PubMedCrossRefGoogle Scholar
  11. 11.
    C. A. Kitt, et al., Soc. Neurosci. Abstr., 10: 271 (1984).Google Scholar
  12. 12.
    R. G. Struble, J. C. Hedreen, L. C. Cork, and D. L. Price, Neurobiol. Aging (in press).Google Scholar
  13. 13.
    P. S. Goldman-Rakic and R. M. Brown, Neuroscience, 6: 177–187 (1981).PubMedCrossRefGoogle Scholar
  14. 14.
    R. G. Struble, C. A. Kitt, L. C. Walker, L. C. Cork, and D. L. Price, Brain Res. (in press).Google Scholar
  15. 15.
    R. T. Davis, C. L. Bennett, and R. P. Weisenburger, Percept. Motor Skills, 55:703–709 (1982); R. T. Davis, Exp. Gerontol., 13: 237–250 (1978).CrossRefGoogle Scholar
  16. 16.
    R. G. Struble, L. C. Cork, P. J. Whitehouse, and D. L. Price, Science, 216: 413–415 (1982).PubMedCrossRefGoogle Scholar
  17. 17.
    R. G. Struble, D. L. Price Jr., L. C. Cork, and D. L. Price, Senile plaques in the neocortex of aged monkeys (submitted for publication).Google Scholar
  18. 18.
    E. K. Perry et al., Br. Med. J., 2: 1457–1459 (1978).PubMedCrossRefGoogle Scholar
  19. 19.
    P. Davies, R. Katzman, and R. D. Terry, Nature, 288:279–280 (1980); M. Rossor et al., Brain Res., 201:249–253 (1980); M. N. Rossor, P. C. Emson, L. L. Iversen, C. Q. Mountjoy and M. Roth, in: Alzheimer’s Disease: Advances in Basic Research and Therapies. Proceedings of the Third Meeting of the International Study Group on the Treatment of Memory Disorders Associated with Aging, R. J. Wurtman, S. H. Corkin and J. H. Growdon, Eds. (Zurich, 1984 ), pp. 29–37.PubMedCrossRefGoogle Scholar
  20. 20.
    E. K. Perry and R. H. Perry, in: Alzheimer’s Disease, B. Reisberg, Ed. ( The Free Press, New York, 1983 ), pp. 93–99.Google Scholar
  21. 21.
    The authors gratefully acknowledge discussions with Drs. Peter J. Whitehouse, John C. Hedreen, Mahlon R. DeLong, Susan J. Mitchell, Richard M. Zweig, Juan C. Troncoso, John W. Griffin, and Paul N. Hoffman. Drs. Ludwig Sternberger, Nancy Sternberger, Bruce Wainer, and Douglas Murphy provided antibodies for some of the original studies described in this review. Mr. Richard Altschuler and Mark Becher and Ms. Barbara Holden and Eleanor Brown provided technical assistance. Mrs. Carla Jordon prepared the manuscript. This work was supported by grants from the U.S. Public Health Service (AG 03359, AG05146, NS 20471, NS 10580, NS 15721, NS 07179) and funds from Point of View Inc. and the Hurd Foundation.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Donald L. Price
    • 3
    • 4
  • Robert G. Struble
    • 1
  • Cheryl A. Kitt
    • 1
  • Linda C. Cork
    • 2
  • Lary C. Walker
    • 1
  • Manuel F. Casanova
    • 1
  • Richard E. Powers
    • 1
  1. 1.Neuropathology Laboratory Department of PathologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Division of Comparative MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of NeurologyThe Johns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of NeuroscienceThe Johns Hopkins University School of MedicineBaltimoreUSA

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