The Serpin, α1-Antichymotrypsin, in Brain Aging and Diseases of the Nervous System

  • Carmela R. Abraham
  • Huntington Potter
Part of the NATO ASI Series book series (NSSA, volume 191)


One of the main neuropathological lesions that characterize the brains of Alzheimer disease patients is the neuritic or senile plaque, which consists of a spherical core of extracellular protein filaments surrounded by a halo of degenerating nerve cell processes. Extracellular protein filaments similar to those in the cores of neuritic plaques also occur in the walls of meningeal and intracortical blood vessels. The proteinaceous deposits in the cores of neuritic plaques and in blood vessels are referred to by the generic term “amyloid” generally defined as an aggregate of extacellular 6–10 nm protein filaments that has certain tinctorial properties.


Amyloid Deposit Cerebral Amyloid Angiopathy Neuritic Plaque Amyloid Protein Alzheimer Disease Patient 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G.G. Glenner, and C.W. Wong, Alzheimer’s disease-initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 122: 885–890 (1984).Google Scholar
  2. 2.
    C.L. Masters, G. Multhaup, G. Simms, J. Pottgieser, R.N. Martins, and K. Beyreuther, Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 4: 2757 (1985).Google Scholar
  3. 3.
    C.W. Wong, V. Quaranta, and G.G. Glenner, Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proc. Natl. Acad. Sci. USA 82: 8729–8732 (1985).CrossRefPubMedGoogle Scholar
  4. 4.
    D.J. Selkoe, C.R. Abraham, M.B. Podlisny, and L.K. Duffy, Isolation of low-molecular weight proteins from amyloid plaque fibers in Alzheimer’s disease. J. Neurochem. 46: 1820–1834 (1986).CrossRefPubMedGoogle Scholar
  5. 5.
    D. Goldgaber, M.J. Lerman, O.W. McBride, V. Saffiotti, and D.C. Gadjusek, Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease. Science 235: 877 (1987).CrossRefPubMedGoogle Scholar
  6. 6.
    J. Kang, H.G. Lemaire, A. Unterback, J.M. Salbaum, C.L. Masters, K.H. Grezeschik, G. Multhaup, K. Beyreuther, and B. Muller-Hill, The precursor of Alzheimer disease amyloid A4 protein resembles a cell-surface receptor. Nature 325: 733 (1987).CrossRefPubMedGoogle Scholar
  7. 7.
    R.E. Tanzi, J.F. Gusella, P.C. Watkins, GA.P. Bruns, P. St. George-Hyslop, M.L. Van Keuren, D. Patterson, S. Pajan, D.M. Kurnit, and R.L. Neve, Amyloid fi-protein gene; cDNA, mRNA distributions, and genetic linkage near the Alzheimer locus. Science 235: 880 (1987).CrossRefPubMedGoogle Scholar
  8. 8.
    N.K. Robakis, N. Ramakrishna, G. Wolfe, and H.M. Wisniewski, Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc. Natl. Acad. Sci. USA 84: 4190 (1987).CrossRefPubMedGoogle Scholar
  9. 9.
    C.R. Abraham, D.J. Selkoe, and H. Potter, Immunochemical identification of the serine protease inhibitor al-antichymotrypsin in the brain amyloid deposits of Alzheimer’s disease. Cell 52: 487–501 (1988).CrossRefPubMedGoogle Scholar
  10. 10.
    H.M. Wisniewski, and R.D. Terry, Morphology of the aging brain, human and animal. In: Progress in Brain Research, 1973; Vol. 40, Neurobiological Aspects of Maturation and Aging ed. D.H. Ford, pp. 1108–1109. Amsterdam: Elsevier.Google Scholar
  11. 11.
    R.G.Struble, D.L. Price, Jr., L.C. Cork, and D.L. Price, Senile plaques in cortex of aged normal monkeys. Brain Res. 361: 267–275 (1985).CrossRefGoogle Scholar
  12. 12.
    D.J. Selkoe, D.S. Bell, M.B. Podlisny, D.L. Price, and L.C. Cork, Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer’s disease. Science 235: 873–877 (1987).CrossRefPubMedGoogle Scholar
  13. 13.
    T.I. Mandybur, The incidence of cerebral amyloid angiopathy in Alzheimer’s disease. Neurology 25: 120–126 (1975).CrossRefPubMedGoogle Scholar
  14. 14.
    M. Tomonoga, Cerebral amyloid angiopathy in the elderly. J. Amer. Geriatr. Soc. 29: 151–157 (1981).Google Scholar
  15. 15.
    C.L. Joachim, L.K. Duffy, J. Morris, and D.J. Selkoe, Protein chemical and immunocytochemical studies of meningovascular p-amyloid protein in Alzheimer’s disease and normal aging. Brain Res., 474: 100–111 (1988).Google Scholar
  16. 16.
    A. Weidemann, G. König, D. Bunke, P. Fischer, C.L. Masters, and K. Beyreuther, Identification, biogenesis and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 57: 115126 (1989).Google Scholar
  17. 17.
    D.L. Justice, R.H. Rhodes, and ZA. Tokes, Immunohistochemical demonstration of proteinase inhibitor at-antichymotrypsin in normal human central nervous system. J. Cell. Biochem. 34: 227–238 (1987).CrossRefPubMedGoogle Scholar
  18. 18.
    J. Travis, J. Bowen, and R. Baugh, Human arantichymotrypsin: interaction with chymotrypsin-like proteinases. Biochemistry 17: 5651–5656 (1978).CrossRefPubMedGoogle Scholar
  19. 19.
    P. Ponte, P. Gonzalez-DeWhitt, J. Schilling, J. Miller, D. Hsu, B. Greenberg, K. Davis, W. Wallace, I. Lieberburg, F. Fuller, and B. Cordell, A new A4 amyloid mRNA contains a domain homologous to serine protease inhibitors. Nature 331: 525–527 (1988).CrossRefPubMedGoogle Scholar
  20. 20.
    R.E. Tanzi, A I McClatchey, E.D. Lamberti, L. Villa-Komaroff, J.F. Gusella, and R.L. Neve, Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease. Nature 331: 528–530 (1988).CrossRefPubMedGoogle Scholar
  21. 21.
    N. Kitaguchi, Y. Takahashi, Y. Tokushima, S. Shiojiri, and H. Ito, Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 331: 530–532 (1988).CrossRefPubMedGoogle Scholar
  22. 22.
    E.M. Castano, and B. Frangione, Biology of disease: Human amyloidosis, Alzheimer disease and related disorders. Lab. Invest. 58: 122–132 (1988).PubMedGoogle Scholar
  23. 23.
    S.G. Van Duinen, E.M. Castano, F. Prelli, G.TA. Bots, W. Luyendijk, and B. Frangione, Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer’s disease. Proc. Natl. Acad. Sci. 84: 5991 (1987).CrossRefPubMedGoogle Scholar
  24. 24.
    J. Ghiso, O. Jensson, and B. Frangione, Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of y-trace basic protein (cystatin C). Proc. Natl. Acad. Sci. 83: 2974–2978 (1986).CrossRefPubMedGoogle Scholar
  25. 25.
    H. Baumann, G.P. Jahreis, D.N. Sauder, and A. Koj, Human keratinocytes and monocytes release factors which regulate the synthesis of major acute-phase plasma proteins in hepatic cells from man, rat and mouse. J. Biol. Chem. 259: 7331 (1984).PubMedGoogle Scholar
  26. 26.
    H. Baumann, C. Richards, and J. Gauldie, Interaction among hepatocyte-stimulating factors, interleukin 1, and glucocorticoids for regulation of acute phase plasma proteins in human hepatoma (HepG2) cells. J. Immunol. 139: 4122–4128 (1987).Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Carmela R. Abraham
    • 1
  • Huntington Potter
    • 1
  1. 1.Department of NeurobiologyHarvard Medical SchoolBostonUSA

Personalised recommendations