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Description

Apolipoprotein E (UniProt P02649, also known as Apo-E) is encoded by the APOE (also known as AD2, LDLCQ5, LPG) gene (Gene ID 348) in human. Apolipoprotein E (ApoE) is found in the chylomicron and Intermediate-density lipoprotein (IDLs) and is essential for the normal catabolism of triglyceride-rich lipoprotein constituents. ApoE is initially produced with a signal peptide sequence (a.a. 1-18), the removal of which yields the 299 a.a. mature protein. Three additional natural variants (E2, E3, and E4) exist due to polymorphisms. E4 has an allele frequency of approximately 14 percent and has been implicated in atherosclerosis and various CNS disorders, including Alzheimer's disease (AD). ApoE4 is highly susceptible to proteolysis, which impairs its role in cholesterol transport and beta-amyloid removal in the CNS. Various ApoE4 fragments (14-20 kDa) have been identified in the AD brain. The C-terminal portion of apoE has been implicated in binding to beta-amyloid and is localized to plaques, while the N-terminal domain preferentially localizes within neurofibrillary tangles (NFTs) in the AD brain.