THE INTRACELLULAR FATE OF APOLIPOPROTEIN-E IS TAU-DEPENDENT AND APOE ALLELE-SPECIFIC

THE apolipoprotein E (apoE) gene has been identified as a susceptibili ty gene for Alzheimer's disease, although the mechanism whereby apoE e xerts this effect has not been determined. The aim of this study was t o examine the intracellular fate of apoE and we demonstrate that in ma mmalian cells-transiently expressing tau and the low density lipoprote in 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 a nd, although tau phosphorylation was not affected by apoE, these resul ts suggest that apoE interactions with the cytoskeleton might be impor tant in the molecular pathogenesis of Alzheimer's disease.