Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease

Cell. 1988 Feb 26;52(4):487-501. doi: 10.1016/0092-8674(88)90462-x.


Two approaches--molecular cloning and immunochemical analysis--have identified one of the components of Alzheimer's disease amyloid deposits as the serine protease inhibitor alpha 1-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 alpha 1-antichymotrypsin. Antisera against purified alpha 1-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 alpha 1-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, alpha 1-antichymotrypsin is expressed in Alzheimer brain, particularly in areas that develop amyloid lesions. Models by which alpha 1-antichymotrypsin could contribute to the development of Alzheimer amyloid deposits are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Base Sequence
  • Brain / enzymology*
  • Brain / physiology
  • Cloning, Molecular
  • DNA / genetics
  • Humans
  • Immunohistochemistry
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / immunology
  • alpha 1-Antichymotrypsin / genetics
  • alpha 1-Antichymotrypsin / immunology
  • alpha 1-Antichymotrypsin / metabolism*


  • Amyloid
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • alpha 1-Antichymotrypsin
  • DNA

Associated data

  • GENBANK/M18906
  • GENBANK/M22533