Dear Doctor Column, July 31, 2006
Genetic Testing for Alzheimer Disease
Question:
My 86-year-old mother is in the middle stages of Alzheimer disease. We never thought this would happen to our family. Is there a genetic test for relatives of Alzheimer patients?
Answer:
Except under very specific conditions, which don't apply to the vast majority of people with a relative affected by Alzheimer disease (AD), currently available genetic tests cannot tell you what you want to know - whether or not you or your family members will develop the disease later in life.
This highlights one of the major drawbacks often found with genetic testing. Complex chronic conditions such as AD usually result from many interrelated factors, both genetic and environmental. For these conditions, genetic testing sometimes can identify genetic risk factors that increase likelihood of developing a disease, but the tests can't provide definitive answers. The other major problem with genetic testing for AD is that there are no proven options for prevention, no cure for the disease, and few effective treatments for symptoms.
Research has linked mutations in three genes to an uncommon form of AD that often runs in families and strikes people at relatively young ages, typically before they reach 60 years. People who have mutations in any one of these genes, called APP, PS1, and PS2, will develop early-onset AD, which accounts for 1% to 6% of all cases of AD. A small subset of early-onset AD, about 13%, is called familial autosomal dominant AD, a name that describes its pattern of inheritance. With autosomal dominant conditions, all children of parents with the mutation have a 50/50 chance of developing the disease.
Almost everyone with mutations in the APP, PS1, or PS2 genes develops early-onset AD, and up to 70% of patients with this form of AD have mutations in one of these genes. Because a third of patients with early-onset AD don't have abnormalities in these genes, there must be additional genes or environmental factors linked to the condition that scientists have not yet identified. While a genetic test showing you have a mutation in one of these genes can accurately predict development of AD, it cannot rule out the disease. If genetic testing does not find mutations in the APP, PS1, or PS2 genes, you could still develop AD; your risk is the same as the general population - people whose families do not have a history of early-onset AD.
If you have a family member who developed AD before age 60, you might want to consider consulting with a genetic counselor. These professionals are trained in genetic risk assessment and can examine your family's medical history, evaluate your risk for carrying one of the known mutations that causes early-onset AD, and explain how risks and benefits of genetic testing might affect you and your family.
Late-onset AD, which usually develops after age 65, accounts for more than 90% of all cases of the disease. Scientists don't know what causes late-onset AD and the condition doesn't show an obvious inheritance pattern. However, research has identified certain genetic factors that appear to confer a higher degree of risk for the condition.
One of these factors is the apolipoprotein E (APOE) gene, which comes in three different forms, or alleles ─ APOE ε2, APOE ε3, and APOE ε4. People inherit one APOE allele from each parent. Having one or two copies of the ε4 allele increases risk for AD, but doesn’t necessarily mean a person will develop the disease. There is no way to predict with absolute certainty if a person with the ε4 allele will or will not develop AD. More than half of people with an ε4 allele do not develop AD, and many people without the ε4 allele develop the disease.
The accuracy and value of APOE testing is a subject of intense debate and study. Because such testing cannot provide definite answers, most advisory groups do not recommend APOE testing in healthy individuals. Outside of research, the test is almost always used to strengthen a diagnosis of AD in people with confirmed dementia.
All genetic testing raises complex legal and social issues. If a genetic test shows you are at risk for a certain condition, you could be open to discrimination by employers or insurance companies. While there is no federal legislation regarding genetic discrimination in individual insurance coverage or in the workplace, most states have regulations protecting against this type of bias, although none of these laws are comprehensive. If you would like to know more about the laws in your state, please visit the National Conference of State Legislatures web site. It's also important to keep in mind that when one person in a family decides to get tested, results often affect their relatives. Some people may want to know about their risk, while others may not.
Until scientists develop more accurate tests or find effective ways to prevent or treat AD, genetic testing for the condition offers only limited, difficult-to-interpret information and is not likely to be offered in clinical practice. If you are interested in seeking the advice of a genetic counselor, visit the National Society of Genetic Counselors. Click on "Find a Counselor" to locate a professional in your area.
Research in AD is evolving rapidly. To learn more about the disease, diagnosis, patient care, caregiver needs, long-term care, and research, visit the National Institutes on Aging Alzheimer's Disease Education and Referral Center. The Alzheimer's Association is another valuable source that can point you toward local resources and services, support groups, and educational programs.