APOE
Apolipoprotein E
Gene Number: 348
Location: 19q13.32
Key Functions: Lipid transport, cholesterol metabolism, neuronal repair, cardiovascular and neurological health
APOE encodes apolipoprotein E, a multifunctional protein that plays a central role in lipid transport, cholesterol homeostasis, and neuronal maintenance. It is essential for the redistribution of cholesterol and phospholipids between cells, which supports membrane integrity, myelin formation, and synaptic repair in the central nervous system. APOE also regulates lipid metabolism in the liver and peripheral tissues, influencing circulating cholesterol levels and cardiovascular risk.
APOE function impacts:
Lipid transport and metabolism: Mediates the uptake and clearance of lipoproteins, particularly very-low-density and high-density lipoproteins (VLDL and HDL), thereby influencing plasma lipid profiles and atherosclerotic risk.
Neuronal maintenance and repair: Promotes neuroplasticity, supports repair of damaged neurons, and assists in clearing amyloid-beta peptides, a process critical in Alzheimer’s disease prevention.
Cardiovascular health: Modulates vascular lipid deposition and inflammation, affecting susceptibility to coronary artery disease and stroke.
Cognitive function: APOE isoforms influence synaptic stability, neuronal resilience, and overall risk for neurodegenerative disorder
Clinical relevance:
The ε4 allele is associated with increased risk of Alzheimer’s disease, accelerated cognitive decline, higher LDL cholesterol levels, and elevated cardiovascular risk.
The ε2 allele may provide partial protection against Alzheimer’s disease and cardiovascular disease but can sometimes be linked to type III hyperlipoproteinemia in homozygotes.
The ε3 allele is the most common and considered the neutral or reference form, maintaining balanced lipid metabolism and moderate neuroprotective function.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs429358 | No matching variant or no valid DNA data | C | No interpretation available |
rs7412 | No matching variant or no valid DNA data | T | No interpretation available |
rs429358
TT – Associated with ε2 or ε3 status (normal to protective baseline; see combined diplotype block below) (R).
TC – Heterozygous ε4 carrier; ~3× increased risk for late-onset Alzheimer’s disease vs ε3/3 (R).
CC – ε4/ε4; ~12× higher risk for late-onset Alzheimer’s, and dramatically increased risk of early-onset AD (R).
Functional effect: The C allele creates the detrimental ε4 isoform, impairing amyloid-β clearance and increasing cognitive decline and AD vulnerability.
rs7412
CC – Corresponds to ε4 or ε3 depending on rs429358; baseline context for Alzheimer’s/generally neutral risk (R).
CT – Heterozygous ε2 carrier; modestly protective against AD and often associated with favorable lipid profiles (R).
TT – ε2/ε2; most protective genotype for AD risk, though linked to type III hyperlipoproteinemia (R).
Functional effect: The T allele generates the protective ε2 isoform, enhancing lipid clearance and reducing Alzheimer’s risk—but can predispose to type III hyperlipoproteinemia in homozygous state.
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