ApoE Genotype Test

The APOE gene on chromosome 19q13.32 encodes apolipoprotein E, a ligand for the LDL and related receptors that governs clearance of triglyceride-rich lipoproteins and distributes lipids and cholesterol within the central nervous system. The three common protein isoforms differ at two amino-acid positions (residues 112 and 158), where cysteine or arginine substitutions determine receptor-binding affinity and lipid-handling behaviour. These isoforms arise from two coding single-nucleotide polymorphisms (rs429358 and rs7412), and the combination inherited from each parent defines the diploid genotype.

ApoE genotype is a constitutional risk modifier rather than a measure of current physiology. The ε4 allele is associated, in a broadly dose-dependent fashion, with higher plasma LDL cholesterol, accelerated atherosclerosis, and substantially increased risk of late-onset Alzheimer's disease; the ε2 allele is associated with lower Alzheimer's risk but, in the ε2/ε2 state and usually with a second metabolic trigger, predisposes to type III hyperlipoproteinaemia (dysbetalipoproteinaemia). Genotype informs how aggressively measured lipids are managed and how cognitive risk is contextualised, but it never establishes a diagnosis on its own.

ε4 dosage summarises the genotype as the count of the higher-risk allele a patient carries. Because apolipoprotein E4 binds receptors and handles lipids differently from the E3 isoform, biological effect scales approximately with the number of E4 copies expressed, which is why carriage is often reported as none, one, or two copies alongside the full genotype.

Expressing the result as ε4 dosage helps the clinician gauge the magnitude of risk conferred: a single ε4 copy raises late-onset Alzheimer's risk severalfold over ε3/ε3, while two copies raise it considerably more and lower the typical age of onset. The same gradient applies, more modestly, to LDL cholesterol and cardiovascular risk.