Effects of apolipoprotein E (apoE) isoforms, β-amyloid (Aβ) and apoE/Aβ complexes on protein kinase C-α (PKC-α) translocation and amyloid precursor protein (APP) processing in human SH-SY5Y neuroblastoma cells and fibroblasts

We investigated the effects of different apolipoprotein E (apoE) isoforms, A beta (1-42), and apoE/A beta complexes on PKC-alpha translocation and APP processing in human SH-SY5Y neuroblastoma cells and fibroblasts. Treatment of cells with either 10 nM apoE3 or apoE4, 10 muM A beta (1-42), or apoE/A beta complexes induced significant translocation of PKC-alpha in both cell types. Effects were seen using both human recombinant apoE and apoE loaded into P-very low density lipoprotein (P-VLDL) particles. Time course (5-24 h) studies of APP processing revealed that some conditions induced transient or moderate increases in the secretion of proteins detected by 22C11. In contrast, the secretion of alpha -secretase cleaved APP was either not modified or transiently decreased, as determined by immunoblotting with the antibody 6E10. These results suggest that apoE, AP (1-42) and apoE/A beta complexes can modulate PKC activity but do not have major consequences for APP processing. These effects could contribute to the reported PKC alterations seen in AD. However, it is unlikely that the contribution of different apoE isoforms to AD pathology occurs via effects on APP processing. (C) 2001 Elsevier Science Ltd. All rights reserved.