At a glance

Also known as

Apo E genotyping

Why get tested?

To help confirm a diagnosis of Type III hyperlipoproteinaemia (also known as dysbetalipoproteinaemia); occasionally to help confirm a diagnosis of late onset Alzheimer's disease (AD) in a symptomatic adult

When to get tested?

If your doctor suspects that your high cholesterol and triglyceride levels may be due to a genetically inherited disorder, or if you have xanthomas (yellowish raised patches) on your skin

Sample required?

A blood sample drawn from a vein in your arm
 

Confused about genetics?
See our Genetics Information page

What is being tested?

Apolipoprotein (Apo) E is produced under the direction of the APOE gene, is produced primarily in the liver and brain and has two primary metabolic roles:

  1. The transport of lipids from where they are made or absorbed to the tissues where they are stored.
  2. The transport of cholesterol and other lipids from the body's organs to the liver for excretion. ApoE also plays a role in lipoprotein metabolism. It helps clear very low-density lipoprotein (VLDL) and chylomicrons, the large lipoproteins that are responsible for the initial transport of dietary lipids to the liver, from the bloodstream.

This test looks at a person's DNA to determine what combination of APOE forms (genotype) are present. The APOE gene exists in three different forms (alleles) – e2, e3, and e4 – with e3 being the most common allele, found in 60 per cent of the general population. Everyone inherits two APOE genes, one from each parent, that is some combination of these three forms, e.g. e2/e2, e2/e4, e3/e4.

APOE e3/e3 is the most common genotype. APOE e4 (e4/e4 and e4/e3) is found in 25 per cent of the population and is associated with higher LDL-C ("bad cholesterol") and an increased risk of atherosclerosis. 

People with the APOE e2 allele tend to have lower LDL-C levels but elevated triglycerides. APOE e2/e2 is also associated with type III hyperlipoproteinaemia/hyperlipidaemia (HPL III or familial dysbetalipoproteinaemia), a rare inherited disorder that causes fatty yellowish deposits on the skin called xanthomas, increased triglycerides in the blood, and atherosclerosis. Less than 20 per cent of people with e2/e2 develop type III, and usually requires other factors such as obesity or diabetes in order to develop.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in your arm.

The Test

How is it used?

APOE genotype is sometimes used as part of follow-up testing if high cholesterol and triglyceride concentrations are found, to check if a particular lipid abnormality has been genetically inherited. It is not widely used, but when it is requested, it may be in combination with other tests, such as lipoprotein electrophoresis.

When is it requested?

APOE genotyping is sometimes requested when a patient has significantly elevated cholesterol and triglyceride levels that do not respond to changes in the patient's lifestyle (dietary and exercise patterns); when a patient presents with xanthomas (yellowish raised patches) on their skin and the doctor suspects Type III hyperlipoproteinaemia; or when family members have APOE e2/e2 and a doctor wants to see if the patient may be at a higher risk for early heart disease.
 

What does the test result mean?

Patients with APOE e2/e2 genotype are at a higher risk of premature vascular disease, but they may never develop disease. Likewise, they may have the disease and not have e2/e2 alleles because it is only one of the factors involved. In fact only 1 in 50 people with e2/e2 will ever manifest the disease. Apo E genotyping adds additional information and, if symptoms are present, e2/e2 is diagnostic of Type III hyperlipoproteinaemia (although diagnosis must be made in conjunction with other test results and the patient’s clinical history). Therefore this test is limited and used solely by lipid specialists on rare occasions.

Is there anything else I should know?

Although APOE genotyping is being used clinically by Alzheimer's experts, the most it can provide at this time is additional information about a patient with dementia. A definite diagnosis of Alzheimer's disease can only be made by examining a patient's brain tissue after their death.

APOE genotyping is not available in many laboratories. If your doctor recommends this test, your specimen may need to be sent to a reference laboratory and results may take longer to return than they would from local laboratories.

Alterations in lipid concentrations are only one risk factor for, and do not lead directly to, vascular disease or atherosclerosis. Other factors, such as obesity, diabetes, smoking, high blood pressure and hypothyroidism, may also play a role in whether a person actually develops disease.

Common Questions

My father has been diagnosed with probable late onset AD and his APOE test is negative for e4 alleles. Should his doctor be doing other genetic testing?

No, not at this time. Forty percent of those who do have late onset AD are negative for APOE e4 alleles. While genetic mutations of the PSEN1, PSEN2, and APP genes are associated with AD in a very small number of specific family lines, they tend to be associated with early onset AD, rather than late onset. If your father did not show signs of AD until after the age of 65, then this other genetic testing is not indicated. (If you have a very strong family history of AD, several family members over several generations have had AD, you may want to talk to your father's doctor about family risk factors).

I have a 50-year-old brother with Down syndrome who has been diagnosed with probable Alzheimer's. Does this put me at a higher family risk for AD?

Not necessarily. Most people who have Down syndrome will eventually have some degree of Alzheimer's disease symptoms. Down syndrome is associated with a lifelong overproduction of amyloid precursor protein; a portion of this protein, called amyloid beta 42 peptide (Aß42), is associated with the formation of senile plaques (areas of dead nerve cells and protein deposits in the brain) that are characteristic of AD.

Should everyone have their APOE genotype tested?

No, the test is not intended to be used to screen the general population. It is intended to be used in very specific situations to give a doctor additional information. The majority of people have APOE e3 and so will tend to have normal lipid metabolism. Most of the people with other APOE combinations will either; never develop significant problems associated with their lipid metabolism, have type III hyperlipoproteinaemia, or develop APOE associated late onset AD.

Is there a reason to test for APOE genotype more than once?

No, not unless your doctor suspects that the first test was in error. A person inherits one copy of the gene from each parent and genotype does not change.


Last Review Date: October 10, 2016