APOE Genotyping, Alzheimer Disease

Formal Name: Apolipoprotein E Genotyping

This article was last reviewed on March 18, 2014. This article was last modified on December 14, 2017.

Were you looking instead for APOE genotyping ordered to evaluate for cardiovascular disease? If
so, see APOE Genotyping, Cardiovascular Disease.

At a Glance

Why Get Tested?

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

When To Get Tested?

When you have progressive symptoms of dementia and your health practitioner wants to
determine the likelihood that this is due to AD

Sample Required?
 A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

What is being 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 an even greater risk
of developing AD. It is important to note, however, that this risk is only relative. Most individuals
with APOE e4 will never develop AD and there are many people with AD who are e4 negative.

How is the sample collected for testing?

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

Is any test preparation needed to ensure the quality of the

sample?
No test preparation is needed.

Common Questions

How is it used?
APOE genotyping is sometimes used as an adjunct test to help in the diagnosis of probable
late onset Alzheimer disease (AD) in symptomatic adults. It is called susceptibility or risk factor
testing because it indicates whether there is an increased risk of AD but is not specifically
diagnostic of AD. 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. Health 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/Aß42 testing.

When is it ordered?

APOE genotyping may be ordered as an adjunct test when an individual has symptoms of
progressive dementia, such as decreasing intellectual ability and language and speech skills,
memory loss, and personality and behavioral changes that are starting to interfere with daily
living. 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 late onset 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 of those who have
e4 alleles will never develop AD. Even in symptomatic people, only about 60% of those with
late onset AD will have APOE e4 alleles.

Is there anything else I should know?

Although APOE genotyping is being used clinically by Alzheimer experts, the most it can
provide at this time is 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.

APOE genotyping is not available in every laboratory. If a health 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?

No, not at this time. Forty percent of those who have late onset Alzheimer disease (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 are associated with
early onset AD, not 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.

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 health practitioner additional information. The majority
of people have APOE e3. Most of the people with other APOE combinations will never develop
APOE-associated late onset AD.

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

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

On This Site
Tests: Tau/Aß42, PSEN1

Conditions: Alzheimer Disease

Elsewhere On The Web

Genetics Home Reference: APOE
Mayo Clinic: Alzheimer's, Is it in your genes?
Alzheimer Research Forum
Alzheimer's Association: What is Alzheimer's
alzheimers.gov: For the people helping people with Alzheimer's
Alzheimer's Disease Education and Referral (ADEAR) Center
ADEAR: Alzheimer's Disease Genetics Fact Sheet
National Institute of Neurological Disorders and Stroke: Alzheimer's Disease Information Page

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