ApoE Genotyping: About Testing
Also known as: Apo E genotyping
Formal name: Apolipoprotein E genotyping
Related tests: Cardiac risk assessment, HDL cholesterol, LDL cholesterol, lipid profile, triglycerides, Tau protein
The Test
How is it used?
ApoE genotyping is sometimes used as part of follow-up testing if high cholesterol and triglyceride levels 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.
ApoE genotyping is also sometimes used to help confirm a diagnosis of probable late onset Alzheimer's disease (AD) in adults with symptoms. It is called 'susceptibility' or 'risk factor' testing because it indicates whether there is an increased risk of developing AD but is not diagnostic of AD. There are no clear-cut tests to diagnose Alzheimer's disease; the best a doctor can do right now is to rule out anything else that may be causing dementia and check for a genetic predisposition to AD (with ApoE genotyping, perhaps in conjunction with Tau/Aß42 testing).
ApoE genotyping is also sometimes used to help confirm a diagnosis of probable late onset Alzheimer's disease (AD) in adults with symptoms. It is called 'susceptibility' or 'risk factor' testing because it indicates whether there is an increased risk of developing AD but is not diagnostic of AD. There are no clear-cut tests to diagnose Alzheimer's disease; the best a doctor can do right now is to rule out anything else that may be causing dementia and check for a genetic predisposition to AD (with ApoE genotyping, perhaps in conjunction with Tau/Aß42 testing).
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.
ApoE genotyping is also sometimes requested when patients have symptoms of progressive dementia, such as decreasing intellectual ability, language and speech skills, memory loss, and personality and behavioural 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 establish a diagnosis of probable Alzheimer's disease.
ApoE genotyping is also sometimes requested when patients have symptoms of progressive dementia, such as decreasing intellectual ability, language and speech skills, memory loss, and personality and behavioural 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 establish a diagnosis of probable Alzheimer's disease.
What does the test result mean?
Patients with ApoE e2/e2 alleles 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. ApoE 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).
Patients who have ApoE e4/e4 are more likely to develop atherosclerosis. Patients who have symptoms of late onset Alzheimer's disease AND have one or more e4 copies of the Apo E gene are more likely to have AD. It is not diagnostic of AD, though, and should NOT be used to screen patients without symptoms or their family members. Many people will have e4 alleles and never develop AD. Even in symptomatic patients, only about 60% of those with late onset AD will have ApoE e4 alleles.
Patients who have ApoE e4/e4 are more likely to develop atherosclerosis. Patients who have symptoms of late onset Alzheimer's disease AND have one or more e4 copies of the Apo E gene are more likely to have AD. It is not diagnostic of AD, though, and should NOT be used to screen patients without symptoms or their family members. Many people will have e4 alleles and never develop AD. Even in symptomatic patients, 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'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 will need to be sent to a reference laboratory and results may take longer to return than they would from other laboratories.
ApoE genotyping is not available in many laboratories. If your doctor recommends this test, your specimen will need to be sent to a reference laboratory and results may take longer to return than they would from other laboratories.
The Test Sample
What is being tested?
The test looks at a patient's DNA to determine what combination of Apo E gene alleles (copies) he or she has. The ApoE gene exists in three different forms - e2, e3, and e4 - with e3 considered to be the normal form. Everyone has a pair of ApoE genes that is some combination of these three, for example e3/e3, e2/e2, e2/e4 etc.
Apolipoprotein (Apo) E is made in the liver and brain and helps transport lipids (fats) from one place to another thus helping to clear dietary fats, such as triglycerides, from the blood.
The e2 form of ApoE is less able to clear lipids from the blood compared to the other forms. This means that if someone has an e2/e2 combination, they may clear dietary fat from their body at a slower rate and be at a higher risk for early vascular disease because of the increased likelihood that the fats will be deposited in the blood vessel walls. It is not a straightforward diagnosis, however, as other factors, such as obesity, diabetes, and hyperthyroidism, may play a role in whether a patient actually develops disease.
The Apo e4 allele has been shown to be associated with an increased risk of late onset Alzheimer's disease (developing after the age of 65). While one copy of e4 constitutes a risk (e2/e4 or e3/e4), two copies of e4 (e4/e4) indicate a greater risk of developing AD, the actual amount of risk involved has not been fully established.
Apolipoprotein (Apo) E is made in the liver and brain and helps transport lipids (fats) from one place to another thus helping to clear dietary fats, such as triglycerides, from the blood.
The e2 form of ApoE is less able to clear lipids from the blood compared to the other forms. This means that if someone has an e2/e2 combination, they may clear dietary fat from their body at a slower rate and be at a higher risk for early vascular disease because of the increased likelihood that the fats will be deposited in the blood vessel walls. It is not a straightforward diagnosis, however, as other factors, such as obesity, diabetes, and hyperthyroidism, may play a role in whether a patient actually develops disease.
The Apo e4 allele has been shown to be associated with an increased risk of late onset Alzheimer's disease (developing after the age of 65). While one copy of e4 constitutes a risk (e2/e4 or e3/e4), two copies of e4 (e4/e4) indicate a greater risk of developing AD, the actual amount of risk involved has not been fully established.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in your arm.
Also known as: ApoE cardiac risk; ApoE 2 mutations; APOE4 genotype
Formal name: Apolipoprotein E genotyping
Related tests: Cardiac Risk Assessment; HDL Cholesterol; LDL Cholesterol; Lipid Profile; Triglycerides; Tau/Aß42
The Test
How is it used?
In Cardiovascular Disease (CVD)
The test for ApoE is not widely used and it's clinical usefulness is still being researched. When it is ordered, it may be used in combination with other lipid tests that evaluate risk for CVD, such as cholesterol levels and lipoprotein electrophoresis. It may sometimes be used to check for and help diagnose a genetic component to a lipid abnormality.
Testing for ApoE may sometimes be ordered to help guide lipid treatment. In cases of high cholesterol and triglyceride levels, statins are usually considered the treatment of choice to decrease the risk of developing CVD. However, there is a wide variability in the response to these lipid-lowering drugs that is in part influenced by the Apo E genotype. Though appropriately responsive to a low fat diet, people with ApoE e4 may be less likely than those with ApoE e2 to respond to statins by decreasing their levels of LDL-C and may require adjustments to their treatment plans. At present, the clinical utility of this type of information is yet to be totally understood. Dietary adjustment and statin drugs are the preferred agents for lipid-lowering therapy. Apo E genotyping may be used to provide supplemental information.
ApoE testing may also be ordered occasionally to help diagnose type III hyperlipoproteinemia in a person with symptoms that suggest the disorder and to evaluate the potential for the condition in other family members.
In Alzheimer's Disease
ApoE genotyping is also sometimes used as an adjunct test to help in the diagnosis of probable late onset Alzheimer's 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 patient has dementia, the presence of ApoE4 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's disease during life. Physicians 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.
The test for ApoE is not widely used and it's clinical usefulness is still being researched. When it is ordered, it may be used in combination with other lipid tests that evaluate risk for CVD, such as cholesterol levels and lipoprotein electrophoresis. It may sometimes be used to check for and help diagnose a genetic component to a lipid abnormality.
Testing for ApoE may sometimes be ordered to help guide lipid treatment. In cases of high cholesterol and triglyceride levels, statins are usually considered the treatment of choice to decrease the risk of developing CVD. However, there is a wide variability in the response to these lipid-lowering drugs that is in part influenced by the Apo E genotype. Though appropriately responsive to a low fat diet, people with ApoE e4 may be less likely than those with ApoE e2 to respond to statins by decreasing their levels of LDL-C and may require adjustments to their treatment plans. At present, the clinical utility of this type of information is yet to be totally understood. Dietary adjustment and statin drugs are the preferred agents for lipid-lowering therapy. Apo E genotyping may be used to provide supplemental information.
ApoE testing may also be ordered occasionally to help diagnose type III hyperlipoproteinemia in a person with symptoms that suggest the disorder and to evaluate the potential for the condition in other family members.
In Alzheimer's Disease
ApoE genotyping is also sometimes used as an adjunct test to help in the diagnosis of probable late onset Alzheimer's 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 patient has dementia, the presence of ApoE4 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's disease during life. Physicians 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 is sometimes ordered when a patient has significantly elevated cholesterol and triglyceride levels that do not respond to dietary and exercise lifestyle changes.
- When family members have ApoE e2/e2 and a doctor wants to see if the person might be at a higher risk for early heart disease.
- When someone has yellowish skin lesions called xanthomas and the doctor suspects Type III hyperlipoproteinemia.
What does the test result mean?
People with ApoE e2/e2 alleles 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. ApoE genotyping adds additional information and, if symptoms are present, e2/e2 can help confirm type III hyperlipoproteinemia.
Those who have ApoE e4/e4 are more likely to have atherosclerosis. People who have symptoms of late onset Alzheimer's disease (AD) AND have one or more ApoE e4 copies of the e4 gene 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.
ApoE e3 has "normal" lipid metabolism, thus may not have any genotype impact.
Those who have ApoE e4/e4 are more likely to have atherosclerosis. People who have symptoms of late onset Alzheimer's disease (AD) AND have one or more ApoE e4 copies of the e4 gene 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.
ApoE e3 has "normal" lipid metabolism, thus may not have any genotype impact.
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 every laboratory. If your doctor recommends this test, your specimen will need to be sent to a reference lab, and results may take longer to return than they would from a local laboratory.
Alterations in lipid concentrations do not lead directly to vascular disease or atherosclerosis. Other factors, such as obesity, diabetes, and hypothyroidism, also play a role in whether a person actually develops disease.
ApoE genotyping is not available in every laboratory. If your doctor recommends this test, your specimen will need to be sent to a reference lab, and results may take longer to return than they would from a local laboratory.
Alterations in lipid concentrations do not lead directly to vascular disease or atherosclerosis. Other factors, such as obesity, diabetes, and hypothyroidism, also play a role in whether a person actually develops disease.
