Apolipoprotein E Screening: Points to Consider
by Beth A. Pletcher, MD, March 1998

• Much has been written lately about Apolipoprotein E screening for Alzheimer's and cardiovascular disease. At first, population screening for the "bad" ApoE allele seemed like a great idea until physicians started to seriously consider the consequences of screening and some of the difficulties in interpreting the results. This has caused us to take a step back and consider some of the benefits and drawbacks of such testing.

• To understand some of the subtleties one needs to consider just what we know and don't yet know about the Apolipoprotein E gene. We know that this gene exists in three major isoforms or common subtypes which have been creatively named apoE2, apoE3 and apoE4 (I don't know what happened to apoE1). Since we have two alleles or copies of each of our autosomal genes there are six different combinations of common alleles found in humans. ApoE4 has been identified to be a risk factor for both late onset Alzheimer's disease and coronary artery disease.

• As far as the risk for Alzheimer's disease (AD) goes, numerous case-control and family studies have shown an association with the apoE4 allele and disease. For a person who carries one copy of the apoE4 allele the relative risk of developing AD is 2 to 4 times the general population risk and the unlucky person who carries two copies of the apoE4 allele has a 5 to 18 fold increased risk of developing AD. That being said, homozygosity for the apoE4 allele is not sufficient to predict the development of AD in any given individual. Furthermore, about half of the cases of AD are not associated with the apoE4 allele at all. So how can this screening test be used in clinical practice?

• At this point in time, apoE4 screening for AD just doesn't make sense for the general population. However, in an individual with early signs of dementia who may benefit from enrollment in drug trials or therapeutic protocols, the finding of an E4/E4 haplotype might be quite helpful.

• Individuals who are homozygous for apoE4 also have a 2 to 4 fold increased risk for coronary artery disease in association with an elevated LDL cholesterol. However, screening heart patients for apoE4 brings up possible concern for AD, which is a serious, unexpected outcome in an individual who has no symptoms of dementia at presentation.