Systemic and local changes in apolipoprotein E (ApoE) quantity have been related with Alzheimer's and other neurodegenerative diseases, showing the relevance of maintaining physiological ApoE levels. However, APOE transcription has not been extensively studied in neural cells. In this report, we study the transcriptional activity of different APOE proximal promoter regions and their binding to nuclear proteins from human neural (astrocytoma and neuroblastoma) and peripheral (hepatoma and lymphoma) cell lines. We define several regions with a negative regulatory effect in all the cells and a region with a strong positive activity in neuroblastoma cells. Additionally, we show that the −219T/G polymorphism produces variations in APOE transcriptional activity, with the G allele showing higher activity.