Oleocanthal, a phenolic component of extra-virgin
olive oil, has been recently linked to reduced risk of
Alzheimer's disease (AD), a
neurodegenerative disease that is characterized by accumulation of β-
amyloid (Aβ) and
tau proteins in the brain. However, the mechanism by which
oleocanthal exerts its
neuroprotective effect is still incompletely understood. Here, we provide in vitro and in vivo evidence for the potential of
oleocanthal to enhance Aβ clearance from the brain via up-regulation of
P-glycoprotein (P-gp) and
LDL lipoprotein receptor related protein-1 (LRP1), major Aβ
transport proteins, at the blood-brain barrier (BBB). Results from in vitro and in vivo studies demonstrated similar and consistent pattern of
oleocanthal in controlling Aβ levels. In cultured mice brain endothelial cells,
oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of (125)I-Aβ40 showed that administration of
oleocanthal extracted from extra-virgin
olive oil to C57BL/6 wild-type mice enhanced (125)I-Aβ40 clearance from the brain and increased the BEI% from 62.0 ± 3.0% for control mice to 79.9 ± 1.6% for
oleocanthal treated mice. Increased P-gp and LRP1 expression in the brain microvessels and inhibition studies confirmed the role of up-regulation of these
proteins in enhancing (125)I-Aβ40 clearance after
oleocanthal treatment. Furthermore, our results demonstrated significant increase in (125)I-Aβ40 degradation as a result of the up-regulation of Aβ degrading
enzymes following
oleocanthal treatment. In conclusion, these findings provide experimental support that potential reduced risk of AD associated with extra-virgin
olive oil could be mediated by enhancement of Aβ clearance from the brain.