Watching a loved one with Alzheimer’s disease (AD) is both sad and frightening, especially for close relatives. The fear of inheriting this disease leads m any people to want to determine definitively whether or not they will inherit the Alzheimer’s gene. Unfortunately for most people, the definitive test does not exist. Fewer than 2% of people with Alzheimer’s disease have an early-onset familial form of AD (onset usually before the age of 60 years) and carry a predictive gene that causes the disease. The siblings and children of these people have a 50% risk of inheriting the gene, and if they do, virtually a 100% chance of developing AD. However, for the other 98% of people living with AD and for their relatives, there is no simple genetic test that can predict the future.

The apolipoprotein E gene (APOE) is often touted as “the Alzheimer’s gene.” Unlike the genes causing early-onset familial AD, APOE is a susceptibility gene. Susceptibility genes influence the risk for disease but do not cause disease. APOE comes in three forms, e2, e3 and e4. Since each human cell contains two copies of this gene, six combinations of APOE genotypes (the genetic makeup) exist, e2e2, e2e3, e3e3, e2e4, e3e4, e4e4. Having an e4 is associated with an increased risk of AD and having two copies increases the risk significantly. The question, however, is whether or not determining one’s APOE genotype is useful.

Except for early-onset familial AD cases, most AD is a complex, multifactorial disease. Risk for AD will be influenced not only by one’s APOE genotype, but also by at least several yet unidentified genes, ethnicity, gender, and probably environmental factors (also yet identified). Therefore, one’s APOE genotype will not definitively predict the likelihood of developing the disease in the great majority of people. An exception to this may be people who carry two copies of APOE e4 who have a very high lifetime risk (meaning that they will probably develop AD sometime in their lifetime if they do not die of something else first). In reality, just having a parent with AD increases one’s risk by two to three times, the same increase associated with carrying an e4.

Since its discovery in 1992, APOE has caused much debate among neurologists and geneticists. Numerous guidelines have come out against using the test either for diagnostic or predictive purposes. These guidelines state that APOE e4 is neither necessary nor sufficient for developing Alzheimer’s disease. In other words, one can develop AD without an APOE e4 or can carry an APOE e4 and never develop the disease. These guidelines also considered the psychological consequences of learning that one is at high risk for developing an incurable disease. Additionally, APOE is also associated with risk for other diseases such as cardiovascular disease and macular degeneration. One’s willingness to learn about risk for AD might mean learning other confusing information also.

Over the last few years, the amount of information on genetic testing available to the public has increased significantly, as has the inquiry into and demand for genetic tests. As a result, researchers at Boston University established a study to examine the psychological consequences of disclosing APOE status to individuals with a family history of Alzheimer’s disease. To date, the study indicates that people do not suffer significant psychological harm. The results of this study are being used as the rationale for offering direct-to-consumer (DTC) genetic testing on the Internet. To order an APOE test through the Internet, all one has to do is send a saliva sample and agree to some pre-test Internet education and post-test phone genetic counseling. None of this needs to be coordinated by a physician.

In addition to guidelines concerning APOE testing, the American College of Medical Genetics and the National Society of Genetic Counseling have written policy statements concerning DTC genetic tests. Both organizations express concern over tests that are ordered without a physician’s knowledge or involvement. Secrets kept from physicians can impair proper care. Additionally, although the REVEAL study indicated no potential harm from learning APOE results, study participants received a great deal of face-to-face counseling both before and after testing. This situation differs significantly from DTC testing.

When considering whether or not to use a DTC test, consumers must weigh the benefits and the risks. The risks of DTC testing can be significant since it is not regulated. The benefits of APOE testing have not been sufficiently demonstrated. Again, just knowing that one has a parent with a disease tells you that you are at increased risk. This risk does not change even if one is APOE e4 negative. Knowing this, one can prepare for the future, financially and with long-term health insurance, and live a heart healthy life. We should all be doing this anyway.

Jill Goldman is a genetic counselor at Columbia University Medical Center’s Sergievsky Center and Taub Institute for Research on Alzheimer's Disease and the Aging Brain. Before coming to Columbia in the fall of 2007, she worked as a genetic counselor for the Memory and Aging Center at the University of California, San Francisco. Jill holds an M.S. in genetic counseling from the University of California, Berkeley, and an M.Phil. in biology from Yale University.

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