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Alzheimer's Disease
  Genetic Testing for People
Without Symptoms of Alzheimer's

By Mignon Fogarty, MS

Reviewed by Jill Goldman, MS, CGC
Last updated February 23, 2001



Healthy people who have family members with Alzheimer's disease may want to pursue genetic testing to find out if they are at risk. However, genetic testing for Alzheimer's disease is only available under very specific circumstances. B
ecause the one gene for which genetic testing is available tends to cause an early onset form of the disease, genetic testing is only appropriate for people who's family members developed Alzheimer's at an early age. In some cases, genetic testing can also be used to confirm a diagnosis of Alzheimer's disease in people who already show symptoms.

 
 
 

Testing for Predictive Genes

Half of all ovarian cancers are found in women over the age of 65.
There are three rare genetic syndromes that cause people to develop Alzheimer's disease at an early age, typically before age 60. These syndromes are caused by mutations in single genes called APP, PS1, and PS2. If one of your parents has a mutation in any of these genes, you have a 50 percent chance of inheriting the mutation and developing Alzheimer's yourself. This pattern of inhertance is called autosomal dominant. By examining your family's medical history, a genetic counselor can often assess your risk of carrying one of these mutations, and can determine whether genetic testing is appropriate for you.

Drawbacks

If you do have a family history of early onset Alzheimer's disease, genetic testing may still not be able to detect the mutation that's causing your family's disease.

  • Clinical genetic testing is currently only available for one of the three known genes – PS1. Testing for the other two genes is available on a research basis only.
  • The three genes for which genetic testing is available only account for about half of the families with Alzheimer's – or about five percent of all cases. Therefore, there must be other genes that have not yet been identified.

The Importance of Testing the Right Family Member

Even if you decide to pursue genetic testing, you may not be the best person in your family to be tested. This is because testing should begin with the family member who is most likely to have a mutation — and that generally means someone who's already been diagnosed with Alzheimer's. The research lab will sequence this person's entire PS1 gene. If they find a mutation, then other family members can be screened for this same mutation. (Screening for a known mutation is generally faster and less expensive than sequencing the entire gene.)

If the lab does not find a mutation in a family member with Alzheimer's disease, then your family's Alzheimer's is not caused by a mutation in the PS1 gene and genetic testing will not be helpful in determining your risk.

Not All Cases of Alzheimer's Disease Result From a Mutated Gene

When looking at your family history of Alzheimer's disease, it is important to keep in mind that Alzheimer's can develop in people who have not inherited a mutated PS1, PS2, or APP gene. In families who have identified a mutation in PS1, even family members who did not inherit this mutation are at risk of developing the disease — the same risk as people in the general population. For this reason, you should keep in mind the age of onset for a family member who you choose to have tested. If they didn't develop the disease until late in life, they are probably not the best person to be tested for a mutation. You and your relatives should also be aware that if you test negative for a mutation that runs in your family, it does not mean that you won't develop the disease, only that you aren't at higher risk than the general population.

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Testing for Susceptibility Genes

Mutations in APP, PS1, or PS2 all virtually guarantee that a person will develop Alzheimer's disease. However, there is a fourth gene – called APOE – that is also involved in determining Alzheimer's risk. The APOE gene comes in three forms, called e2, e3, and e4. Having the e4 version puts people at higher risk of Alzheimer's disease, but does not ensure that they will develop the disease. Because testing for e4 cannot predict who will get the disease, many medical ethicists and geneticists have recommended against testing for APOE in healthy people.

The rationale for not testing for APOE is that over half the people who carry e4 will not develop Alzheimer's and many people who don't carry e4 will still go on to develop the disease; therefore, genetic testing is not very useful. In fact, genetic testing for this gene is only currently available to help confirm doctor's diagnoses of Alzheimer's, and a doctor is required to sign a form that says the patient has dementia before the test can be performed.

 

 

More on Genetic Testing for People With Symptoms of Alzheimer's Disease (Coming Soon)

The Future of Testing for Susceptibility Genes

If you do not qualify for standard genetic testing for the APOE e4 variation, and you still wish to be tested, genetic testing for APOE and the other Alzheimer's genes is sometimes available as part of ongoing research studies. A medical geneticist or genetic counselor may be able to help you find such studies.

Furthermore, ethicist have suggested that testing for susceptibility to Alzheimer's would be much more acceptable if there were a way to prevent the disease. Thus, as researchers make strides towards preventing and treating Alzheimer's, genetic testing for APOE e4 (and other genes for Alzheimer's susceptibility that might be discovered in the future) are likely to be more widely available.

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Issues to Consider

Considering genetic testing for Alzheimer's is complicated by the fact that even if you test positive for a mutation, there is no way to prevent the disease or treat it once it develops. Despite this drawback, some people decide to pursue genetic testing because it helps them plan for the future and relieves anxiety. However, other people find that they simply don't want to know whether they are going to get a disease that they cannot prevent.

Studies in Huntington's disease – which is similar to Alzheimers in that it is autosomal dominant and currently has no prevention or treatment – gives some insight into how people make decisions about genetic testing for these types of diseases. These studies have found that only about 15 to 20 percent of those at risk actually seek out and go through with getting a genetic test.

Meeting with a genetic counselor can help you understand both whether you are eligible for genetic testing and what risks and benefits there are to testing. In addition to meeting with a genetic counselor, it can be helpful to discuss the decision with family members, religious advisors, and possibly other people who have faced the same decision, such as through a support group.

Even if you choose not to have a genetic test for Alzheimer's, you can make legal and financial plans to protect your family's future. The Alzheimer's Association has information to help you with those steps. It is also important to remember that deciding not to be tested is not a permanent decision; you can change your mind at any time as more researchers uncover methods for treatment and prevention.

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Resources

To learn more about testing for Alzheimer's disease, we recommend the Alzheimer's Association Web site.

 

References

Breitner JC. APOE genotyping and Alzheimer's disease. Lancet. 1996 Apr 27;347(9009):1184-5.

Crauford D, Kerzin-Storrar L, Dodge A, Harris R (1989) Uptake of Presymptomatic Predictive Testing for Huntington Disease. Lancet ii 603-605.

Lendon, CL et al. 1997. Exploring the etiology of Alzheimer disease using molecular genetics. JAMA. Mar 12;277(10):825-31

Tyler A, Morris M, Lazaron L et al (1992) Presymptomatic Testing for Huntington Disease in Wales (1987-1990). British Journal of Phychiatry 161: 481-488.

Genetic testing and Alzheimer's disease: Has the time come? Recommendations of the Stanford Program in Genomics, Ethics and Society (1998) Nature Medicine 4, 757-759

Consensus statement: The clinical introduction of genetic testing for Alzheimer disease. An ethical perspective. Post, S.G. et al. (1997) JAMA 277, 832-836. (Summary) Statement of a consensus group supported by the National Human Genome Research Institute and the National Institutes of Health.

Consensus statement: Apolipoprotein E genotyping in Alzheimer's disease. National Institute on Aging/Alzheimer's Association Working Group (1996) Lancet 347, 1091-1095.

Steele, CD. The genetics of Alzheimer disease. Nurs Clin North Am 2000 Sep;35(3):687-94.

Utility of the Apolipoprotein E Genotype in the Diagnosis of Alzheimer's Disease. Mayeux, R et al. (1998) NEJM 338(8), 506-511.

Molecular genetics of Alzheimer's disease. St. George-Hyslop, PH. (2000)Biological Psychiatry 47(3):183-199.

Personal communication, Elan Pharmaceuticals. Michael Boss.

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