The intracellular fate of apolipoprotein E is tau dependent and apoe allelespecific

The apolipoprotein E (apoE) gene has been identified as a susceptibility gene for Alzheimer's disease, although the mechanism whereby apoE exerts this effect has not been determined. The aim of this study was to examine the intracellular fate of apoE and we demonstrate that in mammalian cells-transiently expressing tau and the low density lipoprotein receptor, apoE is taken up from cerebrospinal fluid (CSF) and apoE3, but not apoE4, reaches the cytoplasm. This isoform difference in the intracellular distribution of apoE is dependent upon tau expression and, although tau phosphorylation was not affected by apoE, these results suggest that apoE interactions with the cytoskeleton might be important in the molecular pathogenesis of Alzheimer's disease.