Influence of prednisolone on β-secretase enzyme activity in vitro

Epidemiological studies have shown that anti-inflammatory medications decrease the incidence of Alzheimer's disease (AD). Our previous studies showed that a regimen of prednisolone decreased the amyloid β-protein (Aβ) concentration in the cerebrospinal fluid of AD patients. However, the detailed mechanism by which prednisolone decreased the Aβ concentration is unknown. In the present study we tested whether prednisolone has a direct inhibitory activity against β-secretase by using an in vitro enzyme assay system. β-Secretase, a fluorogenic substrate of β-secretase, and either prednisolone or β-secretase inhibitor were coincubated, and then the increase in fluorescence intensity was monitored. Prednisolone (1×10−3M–1×10−9) had no effect on the β-secretase activity, whereas β-secretase inhibitor inhibited it. This result shows it to be unlikely that prednisolone has an effect on the intracerebral Aβ metabolism via the modulation of β-secretase activity.