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.

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.