Altered β-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. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.