What is Apolipoprotein E (Apo E)?

From the Guidelines

ApoE, or apolipoprotein E, is a protein that plays a crucial role in transporting cholesterol and other fats through the bloodstream, with three common forms or alleles: ApoE2, ApoE3, and ApoE4, which are significant in medicine due to their association with increased risk of developing Alzheimer's disease and cardiovascular conditions 1.

Key Points About ApoE

• ApoE is produced primarily in the liver and brain and exists in three common forms or alleles: ApoE2, ApoE3, and ApoE4.
• Each person inherits one ApoE allele from each parent, determining their ApoE genotype.
• This protein is particularly important for brain health, as it helps maintain and repair neurons.
• ApoE is significant in medicine because certain variants, particularly ApoE4, are associated with increased risk of developing Alzheimer's disease and cardiovascular conditions.
• People with one copy of ApoE4 have about three times the risk of developing Alzheimer's, while those with two copies face approximately 8-12 times the risk.
• The ApoE2 variant, conversely, appears to offer some protection against Alzheimer's.
• Understanding one's ApoE status can provide insight into disease risk, though genetic testing for ApoE is not routinely recommended as lifestyle factors also significantly influence disease development.

Interaction with Diet and Disease Risk

• Research suggests that genetic variants, including ApoE, may modulate the relationship between dietary saturated fats and cardiovascular disease-related biomarkers 1.
• Carriers of the less common APOE4 allele have shown greater fasting plasma lipid responses to saturated fat in the diet than do non-APOE4 carriers.
• This gene-diet interaction has implications for personalized dietary recommendations, highlighting the need for a more tailored approach to nutrition and disease prevention.

From the Research

Definition and Function of Apo E

• Apolipoprotein E (apoE) is a 34 kDa circulating glycoprotein that plays a crucial role in lipid metabolism and transport [(2,3,4,5,6)].
• It is involved in the clearance of triglyceride-rich lipoproteins and cholesterol efflux from lipid-laden macrophages [(2,3,5,6)].
• ApoE has three major isoforms: apoE2, apoE3, and apoE4, which differ by only a single amino acid interchange and have distinct effects on lipid and neuronal homeostasis [(2,3,4,5,6)].

Role of Apo E in Disease

• ApoE4 is a recognized risk factor for Alzheimer's disease, while apoE2 and apoE4 increase the risk for heart disease [(2,3,4)].
• ApoE4 is associated with dyslipidemia and a more pro-atherogenic lipoprotein-cholesterol distribution [(2,3,6)].
• ApoE has been implicated in various other pathologies, including neurodegenerative diseases, infections, and stress-related disorders [(2,3,4,5)].

Structure and Function of Apo E Isoforms

• The structural differences between apoE2, apoE3, and apoE4 affect their binding affinity to the low-density lipoprotein receptor (LDLR) and their lipid-binding ability [(2,3,4,6)].
• ApoE3 is considered the wild-type isoform and operates optimally in promoting clearance of triglyceride-rich lipoproteins [(3,6)].
• ApoE2 and apoE4 have impaired binding to the LDLR, leading to altered lipoprotein metabolism and increased risk of disease [(2,3,6)].