APOE has a single CpG island overlapping with its 3′-exon. APOE circular RNA and full-length mRNA each constitute one third of the total APOE RNA, with truncated mRNAs likely constituting some of the missing fraction. All APOE RNA species had significantly higher expression in AD frontal lobe than in controls, suggesting a possible modified mechanism of gene action for APOE in AD involving also an epigenetically regulated transcriptional program driven by DNA methylation in the APOE CpG island. The gene discussed is APOE; the disease is Alzheimer disease.