Alpha 1-antichymotrypsin in brain aging and disease.
The recent finding (Abraham et al., 1988) that the serine protease inhibitor, alpha 1-antichymotrypsin, is tightly associated with the amyloid deposits of normal aged and Alzheimer's disease brains, suggests a role for this inhibitor in the amyloid deposition. We used immunohistochemistry to analyze the presence of alpha 1-antichymotrypsin in the similar brain amyloid which accumulates in monkeys with increasing age. The earliest alpha 1-antichymotrypsin immunoreactivity was found in cortical perivascular cells before the appearance of either thioflavin S-identifiable amyloid deposits or beta-protein reactivity in vessels. The cortical amyloid, both in senile plaques and vasculature, was seen only several years later, and could be stained for both beta-protein and alpha 1-antichymotrypsin. In addition, we analyzed the association of alpha 1-antichymotrypsin with the other types of amyloidoses. alpha 1-antichymotrypsin antibodies immunolabeled only amyloid deposits that have as their major component the beta-protein: normal aging, Alzheimer's disease, Down's syndrome and in the hereditary cerebral hemorrhage with amyloidosis of Dutch origin (HCHWA-D), but not in Creutzfeldt-Jakob disease, Familial Amyloidotic Neuropathy, primary amyloidosis, or secondary amyloidosis. Lastly, we used immunocytochemistry to identify cells that express alpha 1-antichymotrypsin during brain degeneration. Such immunoreactivity was found in astrocytes near areas of neuronal or tissue loss, in pericytes and in a few neurons, even in diseases with no alpha 1-antichymotrypsin-containing amyloid deposits. In summary, alpha 1-antichymotrypsin is found in three cell types in various brain diseases. In amyloid deposits it is found only in association with the beta-protein, further strengthening its possible role in the processing of the beta-protein precursor or the stability of the beta-protein amyloid deposits.
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 / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D000686:Amyloidosis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D011498:Protein Precursors / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000032:analysis / Q000378:metabolism*
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors; D000514:alpha 1-Antichymotrypsin