Recently, increasing evidence has linked high
cholesterol to the pathogenesis of
Alzheimer's disease (AD), suggesting that
cholesterol may be a target for developing new compounds to prevent or treat AD.
Plant sterols, a group of
sterols enriched in
plant oils, nuts, and avocados, have the structure very similar to that of
cholesterol, and have been widely used to reduce blood
cholesterol. Due to their
cholesterol-lowering property,
plant sterols such as β-
sitosterol may also influence
cholesterol-depending functions including its role in AD development. Using human platelets, a type of peripheral blood cells containing the most circulating
amyloid precursor
protein (APP), this study investigated the effect of β-
sitosterol on high
cholesterol-induced secretion of β
amyloid protein (Aβ). It was found that β-
sitosterol effectively inhibited high
cholesterol-driven platelet Aβ release. In addition, β-
sitosterol prevented high
cholesterol-induced increase of activities of β- and γ-
secretase, two APP cleaving
enzymes to generate Aβ. Additional experiments showed that high
cholesterol up-regulated
lipid raft
cholesterol. This effect of
cholesterol could be suppressed by β-
sitosterol. These findings suggest that β-
sitosterol is able to inhibit high
cholesterol-induced Aβ release probably through maintenance of membrane
cholesterol homeostasis. Given that dietary
plant sterols have the potential of penetrating the blood-brain barrier (BBB), these data suggest that
plant sterols such as β-
sitosterol may be useful in AD prevention.