Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease.
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.
Abraham
C R
CR
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.
Selkoe
D J
DJ
Potter
H
H
D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D001483:Base Sequence; D001921:Brain / Q000201:enzymology* / Q000502:physiology; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000276:immunology; D000514:alpha 1-Antichymotrypsin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000682:Amyloid; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000514:alpha 1-Antichymotrypsin; D004247:DNA