Human apoE is a 34 kDa glycoprotein composed of 299 amino acids and is highly expressed in astrocytes, microglia, and brain vascular mural cells in the CNS. The apoE isoforms encoded by the three corresponding gene alleles differ from one another only at positions 112 and 158 (apoE2: Cys112, Cys158; apoE3: Cys112, Arg158; apoE4: Arg112, Arg158). Upon lipidation by cell surface ABCA1, apoE transports and distributes lipid to neurons and other brain cells through binding to cell-surface apoE receptors, specifically LRP1 and LDL receptor (LDLR), members of the LDLR family. ApoE has two main functional regions: the receptor-binding region in the amino-terminal domain and the lipid-binding region in the carboxyl-terminal domain.