Biochemistry · Protein
Apolipoprotein E (ApoE) !
ApoE is the key that lets chylomicron remnants and IDL into the liver; its variants change cholesterol and Alzheimer risk.
Updated 2026-11-01
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Key facts
- It is on chylomicrons, remnants, VLDL, IDL and some HDL; HDL hands it to new particles.
- It binds the LDL receptor and liver LRP1 to clear remnants.
- Three common alleles: ε2, ε3 (most frequent) and ε4; they differ at residues 112 and 158.
- ApoE2 binds receptors poorly: ε2/ε2 plus a second factor causes dysbetalipoproteinaemia (type III).
- ApoE4 is the main genetic risk factor for late-onset Alzheimer disease.
- Also called
- ApoE
- Genes
- APOE
- Structure (PDB)
- 1NFN
Structure
- A mature 299-residue protein: a four-helix N-terminal domain that binds the receptor (region 136–150) and a lipid-binding C-terminal domain.
- Structure 1NFN is the ApoE3 N-terminal domain: a four-helix bundle.
Regulation
- It is made mainly by the liver, and also by brain astrocytes and macrophages.
- LXR (activated by oxysterols) raises its expression in macrophages.
Inhibitors and toxins
- Not the target of any approved drug.
Clinical notes
- ε2/ε2 plus obesity, diabetes or hypothyroidism: high remnants, palmar xanthomas and early atherosclerosis.
- ε4 is linked to slightly higher LDL and Alzheimer disease; ε2 to lower Alzheimer risk.
- APOE genotyping helps confirm dysbetalipoproteinaemia.
Related conditions
- Familial dysbetalipoproteinemia (type III hyperlipoproteinemia)
- Alzheimer disease
- Atherosclerosis and dyslipidaemia
Related
- Chylomicron
- VLDL (very-low-density lipoprotein)
- HDL (high-density lipoprotein)
- LDL receptor
- Lipoprotein metabolism
Test yourself
Think of the answer, then tap the question to see it.
What does ApoE do on chylomicron remnants?
It is the ligand that binds them to the liver LDL receptor and LRP1 so they are cleared.
Which APOE genotype is linked to dysbetalipoproteinaemia?
ε2/ε2, almost always with a second factor such as obesity, diabetes or hypothyroidism.
Which APOE allele raises the risk of late-onset Alzheimer disease?
ε4.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: APOE: Apolipoprotein E (human) (UniProt, 2026); APOE gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 1NFN: APOLIPOPROTEIN E3 (APOE3) (RCSB Protein Data Bank, 2026); Familial dysbetalipoproteinemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.