The protease inhibitor, alpha 1-antichymotrypsin, is a component of the brain amyloid deposits in normal aging and Alzheimer's disease.
The purpose of this study was to characterize the nature and the origin of the Alzheimer's disease amyloid deposits. We used an amyloid antiserum to screen a human liver expression library. A positive clone was sequenced and found to code for the serine protease inhibitor alpha 1-antichymotrypsin, an acute phase serum protein. Thus, this protein is a second component of the brain amyloid in addition to the beta-protein. In order to determine whether the inhibitor originated from the serum or was made in the brain, we performed Northern blots on tissue from control and Alzheimer brain and found that alpha 1-antichymotrypsin RNA is present in the brain and that the diseased brain contained larger amounts than the controls. Immunocytochemistry and in situ hybridization show the astrocytes to produce the inhibitor, mainly around senile plaques, alpha 1-antichymotrypsin is only associated with the amyloid deposits of the beta-protein kind in normal aging of man and monkeys. Alzheimer's, Down's syndrome and hereditary cerebral hemorrhage with amyloidosis of Dutch origin, but not in primary and secondary amyloidosis or familial amyloidotic polyneuropathy. The specific association between alpha 1-antichymotrypsin and the beta-protein prompted us to suggest a role for this serine protease inhibitor in the proteolytic processing of the beta-protein precursor.
Abraham
C R
CR
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Potter
H
H
D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000096:biosynthesis* / Q000378:metabolism*; D016229:Amyloid beta-Peptides; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000514:alpha 1-Antichymotrypsin