Ordering information

(L) Indicates liquid reagent

Instrument Specific Applications (ISA's) are available for a wide range of biochemistry analysers. Contact us to enquire about your specific analyser.

Physiological Significance

The apolipoproteinE (APOE) gene provides instructions for the production of the apolipoprotein E (apoE) protein. The apoE protein binds with lipid forming lipoproteins which are responsible for the transportation of cholesterol and other lipids through the bloodstream ¹.

Apolipoprotein E (apoE) is a multifunctional glycoprotein with central roles in lipid metabolism, neurobiology, and neurodegenerative diseases. ApoE has three major isoforms (apoE2, apoE3, and apoE4) all of which have different effects on lipid and neuronal homeostasis (fig 1). The key function of apoE is to mediate the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors. These receptors internalise apoE-containing lipoprotein particles and so apoE participates in the distribution or redistribution of lipids among various tissues and bodily cells. The e3 allele is the most of the three and may be considered an ancestral allele. The e4 allele is more common in those of Northern European ancestry and lower in those of Asian ancestry ³.

Cardiovascular Disease

Both apoE2 and apoE4 alleles are associated with cardiovascular disease (CVD).

As apoE2 binds defectively to LDL receptors, apoE2 homozygosity can precipitate type III hyperlipoproteinemia, however, only occurs when another condition, including: diabetes, oestrogen deficiency, hypothyroidism, or obesity, leads to the overproduction of VLDL or fewer LDL receptors, overwhelming the limited ability of apoE2 to mediate the clearance of triglyceride-rich and cholesterol-rich β-VLDL. Other dominant and recessive mutations in apoE that affect residues in or around the receptor binding region also causes type III hyperlipoproteinemia ³.

ApoE3 increases LDL levels in plasma and the risk of atherosclerosis. The lipoprotein-binding preference of apoE4 to large (30-80nm), triglyceride-rick VLDL, is associated with elevated levels of LDL. The enrichment of VLDL with apoE4 accelerates their clearance from the plasma by receptor-mediated endocytosis in the liver and consequently, LDL receptors are downregulated, and LDL levels rise ³.

Neurological Diseases

ApoE4 is the major genetic risk factor, or causative gene, for Alzheimer's disease (AD) and other neurological disorders, including poor clinical outcomes following traumatic brain injury, stroke, frontotemporal dementia, Down syndrome, certain patients with Parkinson's disease, and Lewy body disease ³.

Apo E4 drastically affects AD with 65-80% of all AD patients carrying at least one apoE4 allele. ApoE4 increases the risk of developing AS 4-fold (one allele) and 14-fold (two allele). Carrying one e4 allele is not uncommon with approximately 25% of people worldwide having at least one E4 allele. Fig. 2 illustrates the apoE-mediated pathogenic pathways leading to AD, with amyloid β playing a key role ³.