After receptor-mediated endocytosis of apolipoprotein E (apoE)-containing 
lipoproteins in hepatocytes, the isoform apoE3 is efficiently recycled in a 
process which is associated with cholesterol efflux. Recycling and cholesterol 
efflux are greatly reduced when apoE4 is the only isoform present. ApoE is the 
main apolipoprotein in cerebrospinal fluid, and it plays a pivotal role in 
maintaining cholesterol homeostasis in the brain. The isoform apoE4 is 
associated with an increased risk of Alzheimer's disease and it has been 
postulated that high intracellular cholesterol levels promote the amyloidogenic 
processing of amyloid precursor protein. Therefore we investigated the cellular 
processing of different apoE isoforms as well as the associated cholesterol 
efflux in the murine neuronal cell line HT-22. Uptake of apoE3-containing 
lipoproteins resulted in the expected recycling while, as seen in non-neuronal 
cells, recycling of apoE4 was significantly reduced. However, despite these 
differences in apoE recycling, there was no difference in rates of cholesterol 
efflux. Therefore we conclude that in this neuronal cell model the reduced 
recycling of apoE4 does not affect cellular cholesterol metabolism.