NR AAAR
AU Abraham,C.R.; Potter,H.
TI Alpha 1-antichymotrypsin in brain aging and disease
QU Progress in Clinical and Biological Research 1989; 317: 1037-48
PT journal article; review; review, tutorial
AB 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.
ZR 22
MH Aging/*metabolism; Alzheimer Disease/*metabolism; Amyloid/*metabolism; Amyloid beta-Protein Precursor; Amyloidosis/*metabolism; Brain/*metabolism; Human; Protein Precursors/*metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; alpha 1-Antichymotrypsin/analysis/*metabolism
AD Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
SP englisch
PO USA