In Cardiovascular Disease
ApoE genotyping is sometimes used as part of follow-up testing if high cholesterol and triglyceride levels are found, to check for and help diagnose a genetic component to a lipid abnormality. It is not widely used but, when it is ordered, it may be in combination with other tests, such as lipoprotein electrophoresis.

In cases of high cholesterol and triglyceride levels, statins are usually considered the treatment of choice for cardiovascular disease (CVD). Statins, however, are not sufficient therapy in some susceptible individuals due to a wide variability in lipid-lowering drug response, in part related to Apo E genotype influence. Genetic variation affecting plasma lipoprotein concentrations predicts a therapeutic response that can be used to drive personalized dietary recommendations. Though appropriately responsive to a low fat diet, ApoE e4 individuals are less likely to respond to statins with a commensurate LDL-C lowering effect, unlike ApoE e2 individuals, who have a better therapeutic response to statins. In this light, Apo E genotyping can drive a personalized drug-responsive therapeutic decision tree for CVD.

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. Therefore, if a patient has dementia, the presence of ApoE4 increases the likelihood that the dementia is due to AD. 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, perhaps in conjunction with Tau/Aß42 testing).

ApoE genotyping is sometimes ordered 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 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; or

when a patient presents with xanthomas (yellowish lesions) on their skin and the doctor suspects Type III hyperlipoproteinemia.

ApoE genotyping is also sometimes ordered as an adjunct test when patients have 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’s disease.

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 hyperlipoproteinemia (also known as familial dysbetalipoproteinemia), 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 have atherosclerosis. Patients 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. It is not diagnostic of AD, though, and should NOT be used to screen asymptomatic patients 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.

ApoE e3 has “normal” lipid metabolism, thus no genotype impact.

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 other labs.