What is Apolipoprotein E Genotype?
The APOE gene encodes apolipoprotein E, a 299-amino-acid glycoprotein that mediates binding of lipoproteins to cell-surface receptors and plays a central role in cholesterol transport and clearance. Three common alleles — ε2, ε3, and ε4 — arise from single-nucleotide polymorphisms at codons 112 and 158, producing six possible diplotypes. ApoE3 (the ancestral and most frequent form) binds LDL receptors normally; ApoE2 binds poorly and is associated with higher triglycerides and, in homozygotes, type III dyslipidaemia; ApoE4 increases hepatic LDL receptor expression but is linked to higher LDL cholesterol, impaired neuronal lipid homeostasis, and increased Alzheimer disease risk. Beyond lipid metabolism, ApoE isoforms differ in their effects on neuroinflammation, amyloid-beta clearance, and vascular integrity.