Internalization of ß-Amyloid Causes Downregulation of Apolipoprotein E mRNA Expression in Neuroblastoma Cells

Apolipoprotein (apo) E, like s-amyloid (As), is a key component of the senile plaques that characterize Alzheimer's disease (AD). Understanding how apoE participates in the formation of senile plaques is necessary to clarify the pathogenesis of AD; however, the mechanism remains unknown. In this study, we investigated the changes of cellular apoE and its mRNA level induced by addition of extracellular As to neuroblastoma cells. The presence of ≥1.0 µmol/L of As induced a decrease of apoE mRNA expression and an increase in the immunofluorescence reactivity for intracellular apoE. Both As and apoE were observed by electron-microscopy to be localized within lysosomes. The levels of intracellular apoE and its mRNA returned to the steady state time-dependently. These changes were attenuated by treatments with heparinase I or receptor-associated protein. These findings suggest that the internalized As, along with cellular apoE, induces downregulation of apoE mRNA via a pathway possibly mediated by apoE receptors and heparin sulfate proteoglycans. A disorder of this physiological response could be linked to the development of AD. (received 21 May 2002, accepted 16 July 2002)