Trypsin inhibitor activities of fibroblasts increase with age of donor and are unaltered in familial Alzheimer's disease.
Increasing evidence suggests that proteases and their inhibitors play an important role in the etiology of beta-amyloidogenesis and Alzheimer's disease (AD). It is not clear, however, which proteases and protease inhibitors are responsible for the amyloidogenic proteolysis. Candidates include alpha-1-antichymotrypsin, inter-alpha-trypsin inhibitor, and forms of beta-amyloid precursor protein (beta PP) bearing Kunitz protease inhibitor domains. As one approach to this question, we have determined the trypsin inhibitor activity of fibroblast-like cells from 10 familial AD subjects and 20 controls. The activity was quantitated by measuring remaining trypsin activity of reaction mixtures containing trypsin and cell lysates using a fluorogenic substrate and two physiologically distinct populations of fibroblasts: proliferating cells (grown in the presence of 16% serum) and quiescent cells (maintained in 0.1% serum). The remaining trypsin activities of crude protein extracts from proliferating and quiescent AD cultures were not significantly different from those of controls. Perhaps of more general interest to the biology of aging, however, was our finding that protease inhibitor activity increased with the age of the donor (p = 0.005).
Hearn
M G
MG
Department of Pathology, University of Washington, Seattle 98195, USA.
Edland
S D
SD
Ogburn
C E
CE
Smith
A C
AC
Bird
T D
TD
Martin
G M
GM
Fukuchi
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D014361:Trypsin Inhibitors / Q000378:metabolism*
D014361:Trypsin Inhibitors