Cell
Volume 52, Issue 4, 26 February 1988, Pages 487-501
Journal home page for Cell

Article
Immunochemical identification of the serine protease inhibitor α1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease

https://doi.org/10.1016/0092-8674(88)90462-XGet rights and content

Abstract

Two approaches - molecular cloning and immunochemical analysis - have identified one of the components of Alzheimer's disease amyloid deposits as the serine protease inhibitor α1-antichymotrypsin. An antiserum against isolated Alzheimer amyloid deposits detected immunoreactivity in normal liver. The antiserum was then used to screen a liver cDNA expression library, yielding three related clones. DNA sequence analysis showed that these clones code for α1-antichymotrypsin. Antisera against purified α1-antichymotrypsin stained Alzheimer amyloid deposits, both in situ and after detergent extraction from brain. The anti-amyloid antiserum recognizes at least two distinct epitopes in α1-antichymotrypsin, further supporting the presence of this protein in Alzheimer amyloid deposits. In addition to being produced in the liver and released into the serum, α1-antichymotrypsin is expressed in Alzheimer brain, particularly in areas that develop amyloid lesions. Models by which α1-antichymotrypsin could contribute to the development of Alzheimer amyloid deposits are discussed.

References (101)

  • A. Probst et al.

    Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region

    Brain Res.

    (1983)
  • N.D. Robakis et al.

    Chromosome 21q21 sublocalisation of gene encoding β-amyloid peptide in cerebral vessels and neuritic (senile) plaques of people with Alzheimer disease and Down syndrome

    Lancet

    (1987)
  • D.J. Selkoe

    Altered structural proteins in plaques and tangles: what do they tell us about the biology of Alzheimer's disease?

    Neurobiol. Aging

    (1986)
  • D.J. Selkoe et al.

    Isolation of paired helical filaments and senile plaque amyloid fibers in Alzheimer's disease

    Meth. Enzymol.

    (1986)
  • M. Skinner et al.

    The prealbumin nature of the amyloid protein in familial amyloid polyneuropathy (FAP)-Swedish variety

    Biochem. Biophys. Res. Commun.

    (1981)
  • E.M. Southern

    Detection of specific sequences among DNA fragments separated by gel electrophoresis

    J. Mol. Biol.

    (1975)
  • R.G. Struble et al.

    Senile plaques in cortex of aged normal monkeys

    Brain Res.

    (1985)
  • B.E. Tomlinson et al.

    Observations on the brains of non-demented old people

    J. Neurol. Sci.

    (1968)
  • C.T. Vanley et al.

    Cerebral amyloid angiopathy

    Hum. Pathol.

    (1981)
  • T. Vartio et al.

    Susceptibility of soluble and matrix fibronectins to degradation by tissue proteinases, mast cell chymase and cathepsin G

    J. Biol. Chem.

    (1981)
  • H.M. Wisniewski et al.

    Neurofibrillary tangles of paired helical filaments

    J. Neurol. Sci.

    (1976)
  • A. Alzheimer

    Über eine eigenartige Erkrankung der Hirnrinde

    Allg. Z. Psychiatr. Psych-Gerichtl. Med.

    (1907)
  • P.C. Burger et al.

    The development of the pathological changes of Alzheimer's disease and senile dementia in patients with Down's syndrome

    Am. J. Pathol.

    (1973)
  • T. Chandra et al.

    Isolation and sequence characterization of a cDNA clone of a human antithrombin III

  • T. Chandra et al.

    Sequence homology between human α1-antichymotrypsin, α1-antitrypsin, and antithrombin III

    Biochemistry

    (1983)
  • J.M. Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • F.E. Dwulet et al.

    Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin

  • P. Eikelenbloom et al.

    Immunoglobulins and complement factors in senile plaques: an immunoperoxidase study

    Acta Neuropathol. (Berlin)

    (1982)
  • A.P. Feinberg et al.

    A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity

    Anal. Biochem.

    (1984)
  • R.G. Feldman et al.

    Familial Alzheimer's disease

    Neurology

    (1963)
  • E.J. Furshpan et al.

    Chemical transmission between rat sympathetic neurons and cardiac myocytes developing in microcultures: evidence for cholinergic, adrenergic and dual-function neurons

  • D.C. Gajdusek

    Chronic dementia caused by small unconventional viruses apparently containing no nucleic acid

  • D.C. Gajdusek

    On the uniform source of amyloid in plaques, tangles and vascular deposits

    Neurobiol. Aging

    (1986)
  • J.W. Geddes et al.

    Plasticity of hippocampal circuitry in Alzheimer's disease

    Science

    (1985)
  • J. Ghiso et al.

    Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of γ-trace basic protein (cystatin C)

  • g.G. Glenner

    Alzheimer's disease: multiple cerebral amyloidosis

    Banbury Rep.

    (1983)
  • S. Gloor et al.

    A glia-derived neurite promoting factor with prolease inhibitory activity belongs to the protease nexins

    Cell

    (1986)
  • D.A. Goldberg

    Isolation and partial characterization of the Drosophila alcohol dehydrogenase gene

  • D. Goldgaber et al.

    Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease

    Science

    (1987)
  • P.D. Gorevic et al.

    Isolation and partial characterization of neurofibrillary tangles and amyloid plaque core in Alzheimer's disease: immunohistological studies

    J. Neuropathol. Exp. Neurol.

    (1986)
  • I. Grundke-Iqbal et al.

    Alzheimer neurofibrillary tangles: antiserum and immunohistochemical staining

    Ann. Neurol.

    (1979)
  • G. Gudmundsson et al.

    Hereditary cerebral hemorrhage with amyloidosis

    Brain

    (1972)
  • J. Guenther et al.

    A glia-derived neurite-promoting factor with protease inhibitory activity

    EMBO J.

    (1985)
  • L.L. Heston et al.

    Dementia of the Alzheimer type. Clinical genetics, natural history, and associated conditions

    Arch. Gen. Psychiat.

    (1981)
  • Y. Ihara

    A critical comment of immunocytochemistry of amyloid core in Alzheimer's disease

    Neuropathology

    (1986)
  • Y. Ihara et al.

    Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins

    Nature

    (1983)
  • K. Iqbal et al.

    Alzheimer paired helical filaments: bulk isolation, solubility, and protein composition

    Acta Neuropathol. (Berlin)

    (1984)
  • T. Ishii et al.

    Identification of components of immunoglobulins in senile plaques by means of fluorescent antibody technique

    Acta Neuropathol. (Berlin)

    (1975)
  • T. Ishii et al.

    Immuno-electron-microscopic localization of complements in amyloid fibrils of senile plaques

    Acta Neuropathol. (Berlin)

    (1984)
  • L.F. Jarvik et al.

    Dementia of the Alzheimer type: genetic aspects

  • Cited by (860)

    • Association of α-1-Antichymotrypsin Expression with the Development of Conformational Changes of Tau Protein in Alzheimer's Disease Brain

      2023, Neuroscience
      Citation Excerpt :

      ACT is mainly synthetized in the liver; however, it can also be produced by other organs such as the lungs and brain. In the AD brain, ACT overload has been found in astrocyte cells that are closely associated with different Aβ plaques (Abraham et al., 1988, 1990; Rozemuller et al., 1991; Shoji et al., 1991), and in vitro experiments have demonstrated an increased rate of Aβ-fibril formation in the presence of ACT (Fraser et al., 1993; Eriksson et al., 1995). The overload of ACT in the brain of AD patients may be the result of either vascular distribution through the blood–brain barrier or local overexpression and release by astrocytes cells (Abraham et al., 1988, 1990) and is certainly activated by pro-inflammatory interleukins (Das and Potter, 1995; Machein et al., 1995).

    • Proteinase Inhibitors: Antichymotrypsin

      2021, Encyclopedia of Respiratory Medicine, Second Edition
    View all citing articles on Scopus
    View full text