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 [R].
APOE function impacts [R]:
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.
At GenesUnveiled, your APOE variants contribute to health reports related to late-onset Alzheimer’s risk, brain ageing and lipid / cardiovascular health.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs429358 | Analyze your DNA to see your genotype | C | Analyze your DNA to see a personalized result. |
rs7412 | Analyze your DNA to see your genotype | T | Analyze your DNA to see a personalized result. |
rs429358
TT – Usually indicates ε2 or ε3 haplotypes (no ε4 allele present; see combined APOE diplotype block below)) (R).
TC – Usually tags one ε4 allele (commonly part of an ε3/ε4 or ε2/ε4 genotype; AD risk depends on the full APOE diplotype)3 (R).
CC – Usually tags two ε4-coding haplotypes when paired with rs7412 C/C (ε4/ε4), which is associated with ~12× higher late-onset Alzheimer’s risk vs ε3/ε3 in some studies; see combined block below (R).
Functional effect: The C allele creates the detrimental ε4 isoform, impairing amyloid-β clearance and increasing cognitive decline and AD vulnerability.
rs7412
CC – Usually indicates ε3 or ε4 haplotypes depending on rs429358 (baseline or increased AD risk depending on ε4 status; see combined block) (R).
CT – Usually tags one ε2 allele (ε2/ε3 or ε2/ε4); often linked to slightly more favorable lipid profiles but AD risk depends on the partner haplotype (R).
TT – Usually indicates two ε2-coding haplotypes when combined with rs429358 T/T (ε2/ε2), which tends to be protective for AD (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.
Learn more about what you can do to mitigate risks, and other factors involved by becoming a member of GenesUnveiled today!