A diagnosis of Alzheimer’s disease affects not only individuals, but also their families. Children and other close relatives often fear that they, too, may develop the disabling neurological condition. After all, everyone has heard that Alzheimer’s, like so many other diseases, is “genetic” or “runs in families.” Genetics does play a role, but it’s important to sort out the facts from the misperceptions. Genetic testing may be helpful to some families stricken with Alzheimer’s disease, but in others, it could do more harm than good. Above all, no one should ever be tested without receiving detailed genetic counseling on its potential risks and benefits.
Early And Late Onset
An estimated 10 percent of people over 65 develop Alzheimer’s disease. That means there is an extraordinary number of people today related to a person with Alzheimer’s. Many of them—perhaps you—are wondering, “Will I get it, too?”
Scientists have identified genes that either increase risk for Alzheimer’s or cause the disease outright. The important distinction to make is between cause and risk. Genes directly cause Alzheimer’s disease in a relatively small number of cases, perhaps as few as 2 percent overall. This inherited or “familial” form of Alzheimer’s has been linked to abnormal versions of three genes: presenilin 1 (PS1), presenilin 2 (PS2), and amyloid precursor protein (APP). The hallmarks of early-onset Alzheimer’s are memory impairment and other symptoms that appear in people who are in their 40s or mid-50s. The inheritance pattern of early-onset Alzheimer’s is simple and consistent: If one of your parents has the abnormal gene, there is a 50 percent chance that you do, too. Virtually all people who inherit PS1, PS2, or APP develop Alzheimer’s disease.
The Other 98%
The majority of Alzheimer’s cases occur after age 60. Research has linked risk for developing late-onset or “sporadic” Alzheimer’s disease to a gene called apolipoprotein-E, or APOE. Unlike the genes for early-onset disease, which directly cause illness, APOE is associated only with higher risk for the disease.
APOE itself is not an abnormal or disease-causing gene. Cells use the APOE gene to manufacture a protein, apolipoprotein-E. One of the protein’s possible functions is to help repair connections between brain cells. Everyone inherits two copies of APOE—one from the mother, one from the father. There are three slightly different versions, called APOE-2, APOE-3, and APOE-4. Inheriting one copy of the APOE-4 version increase risk for late-onset Alzheimer’s by two to three times; inheriting two copies of APOE-4 further increases the risk but does not guarantee the person will develop Alzheimer’s.
When an older person is diagnosed with Alzheimer’s disease, their adult children often need reassurance. “Generally, it’s people in their 40s and 50s who have a parent with dementia that is believed to be Alzheimer’s disease,” explains Christina Palmer, Ph.D., a board-certified genetic counselor in Los Angeles and a medical geneticist at UCLA. “They have questions about whether they might develop Alzheimer’s and they wonder if there is a way to find out ahead of time.” The most qualified person to consult is a genetic counselor.
First, the genetic counselor will take a detailed family history. If the family history suggests a pattern of inheritance consistent with early-onset Alzheimer’s, genetic testing may be offered to the family. This will likely be a test for mutations in the PS1 gene linked to most cases of inherited early-onset Alzheimer’s. (The cost of counseling and testing may or may not be covered by insurance.) If the person diagnosed with Alzheimer’s tests positive for a mutation, his or her siblings and children have a 50 percent chance of also testing positive.
At this point in the process, personal choice guides everything, Palmer emphasizes. Family members need to decide if they, too, will have the test and how they will respond to the results. “What would you do different if you have it?” Palmer says. “What would you do if you don’t?” A positive test result could cause psychological distress, and might affect one’s ability to get health or life insurance. Genetic counselors are trained to help people navigate these important questions.
It’s also important to remember that doctors can only test for known mutations that cause early-onset Alzheimer’s. In a family showing the early-onset pattern, a negative test result is not a genetic “all clear.” The culprit may be an as-yet undocumented gene mutation. In these cases, the family could consider enrolling in a research study, if available.
In cases of late-onset Alzheimer’s, genetic testing for the APOE risk gene is not likely—at least right now—to provide useful information. People who inherit APOE-4 are at higher risk, but that does not mean they will develop Alzheimer’s. In fact, up to two-thirds of people who develop Alzheimer’s disease later in life do not have a copy of APOE-4.
Major medical associations, including the American Geriatrics Society (AGS), recommend against testing for APOE-4 in people without any symptoms of dementia, usually meaning the adult children of someone already diagnosed with Alzheimer’s disease. In effect, this means that the vast majority of people should not be tested because they would not benefit if they were.
Doctors may choose to test for APOE in order to help confirm a suspected diagnosis of Alzheimer’s disease. However, even in these cases, the position of the AGS is that APOE testing should not be a “routine” part of evaluating people for Alzheimer’s because it’s possible to diagnose the illness in most cases without genetic testing.
So What CAN You Do?
There is a lot of interest in genetic testing for Alzheimer’s disease. A few years ago, a study by researchers at the Harvard School Of Public Health found that 80 percent of adults in a random telephone survey would take a test if it were accurate. But if there were a 10 percent chance the test could be wrong, only 45 percent said they would take the test.
Right now, genetic testing for late-onset Alzheimer’s is not informative or useful. Genetic counseling, however, is. A counselor can explain what we do and do not know about Alzheimer’s disease, what your family history of Alzheimer’s may mean for you, the limits of genetic testing, and also the potential benefits and consequences of testing—for you, for your family, and for future generations. Although you are not likely to undergo APOE testing, you will probably leave the counselor’s office more informed and less worried.
One final thing: It’s always worth reiterating that genes are not destiny. How you live is just as important as what you draw in the genetic lottery. Research to date suggests that older people who remain physically and mentally active are at less risk overall for dementia.
- The National Society of Genetic Counselors website includes a search engine for finding a member in your area: www.nsgc.org
Facts: About Genes And Alzheimer’s Disease. A publication prepared by the Alzheimer’s Association. Call 800-272-3900 or go to the website: www.alz.org
American Geriatrics Association, Position Statement On Genetic Testing For Late-Onset Alzheimer’s Disease. Go to the website www.AmericanGeriatric.org and follow links: Publications>Guidelines and Position Statements