Altered beta-secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimer's disease brain.
beta-Secretase is the rate limiting enzymatic activity in the production of amyloid-beta peptide, the primary component of senile plaque pathology in Alzheimer's disease (AD). This study performed the first comparative analysis of beta-secretase enzyme kinetics in AD and control brain tissue. Results found V(max) values for beta-secretase to be significantly increased, and K(m) values unchanged in AD temporal cortex compared to matched control temporal cortex. The increased V(max) in AD cases, did not correlate with levels of BACE1, and decreased BACE1 and BACE2 levels correlated with the severity of neurofibrillary pathology (I-VI), and synaptic loss in AD. These results indicate that increased V(max) for beta-secretase is a feature of AD pathogenesis and this increase does not correlate directly with levels of BACE1, the principal beta-secretase in brain.
Stockley
John H
JH
Department of Biochemistry, BioSciences Institute, University College Cork, Cork, Ireland.
Ravid
Rivka
R
O'Neill
Cora
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis
D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human