Altered β‐secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimer's disease brain

Abstract

β‐Secretase is the rate limiting enzymatic activity in the production of amyloid‐β peptide, the primary component of senile plaque pathology in Alzheimer's disease (AD). This study performed the first comparative analysis of β‐secretase enzyme kinetics in AD and control brain tissue. Results found V max values for β‐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 β‐secretase is a feature of AD pathogenesis and this increase does not correlate directly with levels of BACE1, the principal β‐secretase in brain.