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

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 α 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 α 1-antichymotrypsin. Antisera against purified α 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 α 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, α 1-antichymotrypsin is expressed in Alzheimer brain, particularly in areas that develop amyloid lesions. Models by which α 1-antichymotrypsin could contribute to the development of Alzheimer amyloid deposits are discussed.