Isoform-specific effect of apolipoprotein E on endocytosis of beta-amyloid in cultures of neuroblastoma cells.

Investigation of the interactions of nerve cells with human apolipoprotein E (apoE), beta-amyloid (Abeta), and their complex, which are known to be included in senile plaques, is necessary to clarify the functional role of apoE in the pathogenesis of Alzheimer's disease. Using flow cytometric analysis, we investigated the isoform-specific effects of apoE on the endocytosis of Abeta in cultured neuroblastoma cells. The level of internalized Abeta within the cells was dependent on the culture time and the kind of apoE isoform present. Both apoE3 and apoE4 enhanced the internalization of Abeta; however, no difference was observed between their effects. The internalized Abeta was hardly catabolized at all in the presence of apoE4, while rapid clearance of Abeta was observed in the presence of apoE3. Unlike apoE3 and apoE4, apoE2 had no effect on Abeta clearance from the media. The isoform-specific effects of apoE on the endocytosis of Abeta may be implicated in the development of Alzheimer's disease, and if so, each isoform of apoE would induce a different incidence of that disease.