Apolipoprotein E2 (APOE2) (APOE2)

Apolipoprotein E2 (APOE2) is a specific isoform of the Apolipoprotein E protein, distinguished by the presence of cysteine residues at both positions 112 and 158 of the polypeptide chain [1]. It functions primarily as a lipid-binding protein involved in the transport and metabolism of cholesterol and triglycerides in both the systemic circulation and the central nervous system [2]. While APOE2 has a markedly lower affinity for the low-density lipoprotein (LDL) receptor compared to other isoforms, it is highly regarded for its neuroprotective properties, particularly its ability to reduce the risk and delay the onset of Alzheimer's disease [5]. In therapeutic development, APOE2 is being explored as a gene therapy candidate (e.g., LX1001) to counteract the detrimental effects of the APOE4 isoform in the brain [3]. However, individuals homozygous for the APOE2 allele are at an increased risk for Type III hyperlipoproteinemia due to impaired clearance of chylomicron and VLDL remnants [4]. Consequently, drug development targeting or utilizing APOE2 must carefully monitor lipid profiles and potential cardiovascular implications [4].

Other names

Apo-E2APOE-epsilon 2APOE*2Apolipoprotein E isoform 2

Apolipoprotein E2 is utilized in gene therapy to provide neuroprotection by facilitating the clearance of amyloid-beta plaques and modulating lipid metabolism in the brain, effectively competing with or replacing the pathogenic APOE4 isoform [3, 5].