APOE genotyping is not widely used. The clinical usefulness of this test is still being researched, but it may be used as an aid in the diagnosis of probable late onset Alzheimer disease (AD) in a symptomatic adult
APOE Genotyping, Alzheimer Disease
A blood sample drawn from a vein
No test preparation is usually needed. However, prior to testing, you may wish to receive genetic counseling. This could be a helpful and important step in deciding if testing is right for you and for dealing with the result if you decide to be tested.
Apolipoprotein (Apo) E is produced under the direction of the APOE gene and is one of five main types of blood lipoproteins (A-E). This test evaluates a person's DNA to determine what combination of APOE forms (genotype) is present. The APOE gene exists in three different forms (alleles) – e2, e3, and e4 – with e3 being the most common allele, found in 60% of the general population. Everyone inherits a pair of APOE genes that is some combination of these three.
APOE e4 has been associated with an increased risk of late onset Alzheimer disease (AD), that is AD that develops after the age of 65. This effect is additive in that one copy of e4 (e2/e4 or e3/e4) carries some increased risk and two copies of e4 (e4/e4) are associated with even more of a risk of developing AD. It is important to note, however, that we are talking about the risk relative to other people at the same age with fewer copies of e4. In terms of lifetime risk, most individuals with APOE e4 will never develop AD and there are many people with AD who are e4 negative.
How is it used?
APOE genotyping is sometimes used as an added test to help in the diagnosis of probable late onset Alzheimer disease (AD) in symptomatic adults. However, the association of the e4 allele with late onset AD does not mean that it causes AD, only that more people with late onset AD have e4 alleles compared to similar aged peers without late onset AD. For this reason, APOE genotyping is referred to as susceptibility or risk factor testing since it indicates whether there is an increased risk of AD but is not specifically diagnostic of AD. For example, if a person has dementia, the presence of APOE e4 may increase the likelihood that the dementia is due to AD but does not prove that it is.
There are no clear-cut tests to diagnose Alzheimer disease during life. Healthcare practitioners can, however, make a reasonably accurate clinical diagnosis of AD by ruling out other potential causes of dementia and checking for a genetic predisposition to AD with APOE genotyping as supplemental information in conjunction with tau protein and beta amyloid testing.
When is it ordered?
APOE genotyping may sometimes be ordered when an individual has symptoms of progressive dementia, such as:
- Loss of memory that affects daily life—forgetting information that was recently learned. This can occur with normal aging, but the information is usually remembered later. This includes forgetting important dates or events, having to rely on memory aids, and asking for the same information again and again.
- Difficulty planning or problem solving, such as keeping track of bills and payments
- Problems completing usual tasks, such as forgetting how to get to a familiar location
- Confusion about place or time—losing track of time, forgetting where you are or how you got there
- Increasing difficulty reading or judging distances
- Problems speaking or writing—forgetting words, repeating the same thing, struggling with vocabulary
- Losing things more frequently and not being able to logically retrace steps to find them
- Impaired judgment, such as giving away unusually large amounts of money
- Increasing withdrawal from activities, including social, work or family events
- Changes in mood and personality, such as increasing anxiety, fear, suspicion and depression
After non-AD causes, such as overmedication, vascular dementia (caused by strokes), and thyroid disease, have been ruled out, APOE genotyping may help determine the probability that dementia is due to Alzheimer disease.
What does the test result mean?
People who have symptoms of Alzheimer disease (AD) and have one or more APOE e4 copies are more likely to have AD. However, it is not diagnostic of AD and should not be used to screen asymptomatic people or their family members. Many individuals who have APOE e4 alleles will never develop AD. Even in symptomatic people, only about 60% of those with late onset AD will have APOE e4 alleles.
Although APOE genotyping may be used clinically by Alzheimer experts, it can only provide additional information about a person with dementia. A definite diagnosis of Alzheimer disease can only be made by examining a person's brain tissue after their death.
Can this test be done at my local lab?
APOE genotyping is not available in every laboratory. If a healthcare practitioner recommends this test, the specimen will likely be sent to a reference laboratory and results may take longer to return than they would from a local laboratory.
My father has been diagnosed with probable late onset Alzheimer disease and his APOE genotype test is negative for e4 alleles. Should his doctor be doing other genetic testing?
Currently, there are only three known genes that are associated with AD. Mutations in each of these genes (PSEN1, PSEN2, and APP) are associated only with a rare and early onset form of AD. Changes to these genes are not associated with typical or late onset AD. If you have a strong family history of AD that includes multiple family members across several generations, you may want to talk to your doctor about genetic counseling for risk assessment.
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 healthcare practitioner additional information. The association of APOE's e4 allele with AD arose as part of the Framingham Heart study to evaluate genetic risk factors related to cardiovascular health.
Is there a reason to test for APOE genotype more than once?