Neuronal apoptosis is crucial for central nervous system development and also contributes to neurodegenerative disease. Apolipoprotein-E (apoE) regulates brain lipid transport and specific neuronal functions and previous research, investigating non-neuronal cell types, identified an association between apoptosis and increased apoE expression. In the present study we used the human SK-N-SH neuronal cell line to investigate potential changes in apoE expression during apoptosis which occurs as a consequence of extended culture (up to 5 days) without replenishing trophic factors. Standard and real-time PCR analysis indicated a significant 6-fold increase in apoE mRNA after 3 days which was correlated with caspase-3 activation, TUNEL positivity and the formation of apoptotic bodies. ApoE protein levels were low in the absence of apoptosis but increased by 8-fold when apoptosis was induced. Analysis of cellular debris that accumulated in the culture supernatants indicated that apoE levels became progressively concentrated in apoptotic bodies. These data indicate that apoE is up-regulated during neuronal apoptosis and raise the possibility that apoE may play a role in the clearance of apoptotic bodies through apoE-receptor interactions. © 2007 Elsevier Ireland Ltd. All rights reserved.