Alzheimer’s Disease Genetic Testing

Alzheimer's Disease Genetic Testing

Alzheimer’s Disease

What is Alzheimer’s disease?
Alzheimer’s disease is part of a larger group of disorders known as dementia. Dementia is a decline in brain function that is severe enough to interfere with a person’s daily activities and social interactions. Although everyone probably will experience some mental decline with aging, dementia is a more pronounced, progressive loss of mental ability.

Someone with Alzheimer’s disease may show signs of personality change, mood swings, behavioral difficulties, confusion and incontinence. In the later stages of the disease, people become completely dependent on caregivers for their basic needs.

People with Alzheimer’s may live for as long as 20 years after the disease starts. Most patients, however, die eight to 10 years after being diagnosed. A doctor diagnoses someone by looking for a characteristic pattern of symptoms; the disease can only be definitively determined by a brain autopsy after death.

How common is Alzheimer’s disease?
Alzheimer’s disease is the most common cause of dementia, accounting for more than half of all cases in people age 65 and older. Approximately 4 million people in the United States currently suffer from Alzheimer’s.

What is your risk?
Everyone is born with the potential to develop Alzheimer’s disease. Your lifetime risk (to age 85) of developing the disease is about 10%. However, several factors may increase your risk:

  • Age. The older you get, the greater your chance of developing any form of dementia, including Alzheimer’s disease.
  • Family History. If members of your family (especially parents or siblings) have Alzheimer’s or have died from it, your risk of developing the disease could be as high as 50%. Your personal risk depends on a range of factors, including how many family members are affected with Alzheimer’s.
  • Genetic Factors. Some inherited factors may increase your lifetime risk of getting Alzheimer’s disease.

If you are concerned about developing Alzheimer’s disease — either for yourself or a loved-one/member of your family — be sure to meet with your health-care provider.

Is there a cure?
Currently, there is no cure for Alzheimer’s disease. Alzheimer’s disease is an irreversible illness. Some medications, however, may temporarily improve the symptoms of the disease. This may extend the time that people with Alzheimer’s can care for themselves by approximately six months. The most commonly prescribed drugs for this purpose are called cholinesterase inhibitors. Common cholinesterase inhibitors are donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl and Razadyne). Tacrine (Cognex) was the first in this class of drugs, but these others are used now because tacrine can cause liver damage. Memantine, a different type of drug that affects neurotransmitters, is helpful in some patients with moderate to severe Alzehimer’s. Some people benefit from antidepressant medications (for depression but not for dementia).

Researchers looking for methods to prevent or delay the onset of Alzheimer’s are studying antioxidants (such as vitamin E and vitamin C), anti-inflammatory drugs (such as Aleve) and hormone-replacement therapy (estrogen and progesterone). Further research is needed to determine the potential effectiveness of these and other treatments.

What Genes Are Involved in Alzheimer’s Disease?

There are two different categories of genetic risk factors for Alzheimer’s:

Changes in genes for Early-Onset Alzheimer’s almost guarantee that a person will develop the disease. The genes for Early-Onset Alzheimer’s are presenilin-1 (PSEN1), presenilin-2 (PSEN2) and amyloid precursor protein (APP) genes. These changes are extremely rare — only 1% to 2% of Alzheimer’s cases are caused by changes in these genes. These genes changes are the dominant type, meaning that getting one copy of the changed gene is enough to give you the disease.

If your family has several members who developed Alzheimer’s disease at an early age (before age 60 to 65), it is possible (but still not likely) that members of your family carry one of these gene changes. If one of your parents had a change in one of these genes, you have a 50% chance of having the same change, and each of your children has a 50% chance of inheriting it from you. Anyone with one of these gene changes has close to a 100% chance of developing Alzheimer’s disease.

Changes in the apolipoprotein E (APOE) gene for Late-Onset Alzheimer’s will not always cause the disease, but may nudge someone toward developing it. Three forms of the APOE gene are swimming in the gene pool. These forms, called alleles, have been dubbed 2, 3 and 4. Because each person has two copies of the APOE gene, six combinations exist: 2/2, 2/3, 3/3, 2/4, 3/4 and 4/4. Most Americans, approximately 67%, have two copies of the 3 allele (3/3). About 20% are 3/4, and only about 2% are 4/4.

Relative to a 3/3, carrying a 4 allele increases your chances of developing Alzheimer’s. Having two copies of the 4 allele (4/4) triples your chances of getting Alzheimer’s, making your lifetime risk approximately 30% since the usual lifetime risk is about 10%. Having one copy (2/4 or 3/4) increases your lifetime risk, but not as much as having two changes, so the lifetime risk would be around 20%.

Not everyone who carries the 4 allele develops Alzheimer’s. In fact, many people who have the 4 allele never develop the disease, while others who don’t have it do get the disease. For this reason, genetic testing of APOE is not reliable as a predictive test, although it may help to support the diagnosis of someone with early stage Alzheimer’s.

Understanding Test Results And Options

What Is the State of Testing?

Genetic testing for Alzheimer’s disease has a number of limitations:

  • Usefulness. Testing is not useful for most people because most people have Alzheimer’s that is not related to a known genetic factor, or they have Late-Onset Alzheimer’s due to APOE4. Only those with multiple family members who developed Alzheimer’s at young ages (Early-Onset Alzheimer’s) might meet the criteria for genetic testing.
  • Availability. Genetic testing for Alzheimer’s is available only at a few laboratories throughout the country.
  • Risk/Benefit. There are no prevention options for Alzheimer’s. This means if you test positive for the disease, there is no obvious next step or preventive measures you can take. The treatment is the same whether you have a positive genetic test or not.

Genetic testing is available through research studies at a few institutions throughout the country. Generally, results from research studies are not reported to participants in the study unless the results are confirmed in a clinical laboratory. When considering the possibility of participating in such research, you should think about why you want this information and how you think that information would be useful to you. In addition, try to anticipate how you might deal with a test result that does not give you a definitive answer about whether or not you will develop Alzheimer’s.

Testing of asymptomatic adults with a family history of Early-Onset Familial Alzheimer’s Disease (EOFAD) is clinically available for PSEN1, PSEN2, and APP mutations. First, an affected family member would need to be tested to find a mutation. This type of testing can’t predict the age of onset, or severity of symptoms. However, a person with a mutation could expect to develop Early-Onset Alzheimer’s Disease.

How Do You Make Sense Of The Results?

If I test positive for Early-Onset Alzheimer’s, what does that mean for my family and me?
If you don’t have symptoms now, but you inherited a mutation that causes Early-Onset Alzheimer’s disease, you might start having symptoms before age 65. If you have already experienced some of the symptoms, you know how challenging this disease can be. In rare cases, individuals with PSEN2 mutations who are older than 80 have no symptoms of Alzheimer’s.

Because the disease starts later in life, many people who decide to get a genetic test for Alzheimer’s disease already have children. If you test positive, it means your brothers, sisters, and each of your children have a 50 percent chance of having inherited the gene. Your brothers and sisters may want to be tested as well.

According to generally accepted principles of medical ethics, children under 18 should not be tested. A positive test result creates a lot of worry for someone so young. Because there is no treatment for Alzheimer’s disease, the test does not need to be done right away. It’s better to wait until a child turns 18 so he or she can make an independent decision about whether to learn if they have the gene for Alzheimer’s.

Does anyone ever get a positive test result, but not have the disease (a “false” positive)?
The testing laboratory should only call the result abnormal if they are sure the particular change found in your DNA is a definite cause of Alzheimer’s. Occasionally, they may find a change that has never been seen before. If so, they should tell you that the results are not perfectly clear.

Does anyone ever get a negative test result, but actually have the disease (a “false” negative?)
This would not happen as a result of the test. For example, if your affected relative had an Early-Onset Alzheimer’s mutation and you don’t have it, that’s reassuring. However, most people get Alzheimer’s without having a mutation in PSEN1, PSEN2, or APP. So, you can never be guaranteed of not getting Alzheimer’s at all,

Many medical and ethical organizations do not recommend APOE genetic testing to predict the risk of developing Alzheimer’s disease. They believe that until better treatment and prevention methods are available, testing should be done only in rare circumstances and under strict ethical guidelines.

Personal Questions

Why do people get genetic tests?
Some of the reasons you might seek a genetic test are to:

  • Help to prepare your family for possible illness
  • Make decisions about whether you would want to have more children
  • Set up plans for retirement and make changes to wills or insurance policies
  • Gather information that may be relevant to your health and medical care

Even though there is no cure for Alzheimer’s, some people remain interested in genetic testing. Others remain hopeful that a cure or some preventative guidelines for Alzheimer’s will become available in their lifetime. They might want to know if they are at increased risk in case preventive measures become available.

How will I deal with it if the test shows I’m going to develop Alzheimer’s disease?
Learning that you are affected by a serious illness is obviously difficult. Research on the psychological effects of genetic testing for Alzheimer’s disease has shown that people receiving the test results tend to accept the news after a period of adjustment.

Also, it’s not only the people who get positive test results who have trouble adjusting. People who receive a negative test result have reported feeling guilty that they did not get the disease, especially when one of their brothers or sisters was found to carry the gene. Everyone will deal with the information in his or her own way.

Ultimately, you should make sure you have the support of friends, family and professional counselors prepared to help you deal with these issues.

If I have an Early-Onset Alzheimer’s disease gene, can I have children who don’t have it?
Yes. If you have the Alzheimer’s disease gene, you have a 50 percent chance of passing it on to each of your children.

If I don’t have an Early-Onset Alzheimer’s disease gene, my children won’t have it, right?
If you’re not a carrier, then your children cannot inherit the gene from you. Because many people get Alzheimer’s without a change in one of these genes, you can never guarantee your children won’t get Alzheimer’s.

Is there any harm in finding out if I have a gene that causes Early-Onset Alzheimer’s?
Although it is stressful to receive positive test results, most people respond well once they are given time to adjust to the news. The rate of suicide is not dramatically higher among people taking the test as compared to the general population.

The period of adjustment will be, of course, different for different people. For this reason, testing is done through a medical professional who can provide the necessary support to a person struggling to accept this difficult news.

Can a health-insurance company raise my rates or drop me from coverage if I test positive?
In 2008, the U.S. government passed a law called GINA (Genetic Information Nondiscrimination Act). This law prohibits discrimination by health insurers and employers on the basis of genetic information. Learn more here.

Also, this may depend on whether you have group insurance or are self-employed. Both federal and state laws usually cover people with group insurance, while state laws only cover people who are self-employed. Also, the Federal Health Insurance Portability and Accountability Act (HIPAA) of 1996 prohibits health insurance discrimination based on any “health status-related factor” (including genetic information) by group health plans. Unfortunately, this act does not apply to the self-employed.

Life insurance, long-term care and disability insurance are generally not covered by these laws. People with life and disability coverage provided by their employers are unlikely to have this insurance affected by a genetic test result.

What are the implications of genetic testing?
If you are thinking about genetic testing for Alzheimer’s, consider the following:

  • If you get a genetic test, it affects more than just you. The outcome has implications for family members who may not want to know that they are at risk of having inherited or that they have passed on a harmful gene change.
  • If you do not have the altered gene, you may experience anxiety, depression, relief or guilt about a negative test result (especially in cases where close family members or children tested positive). You might also experience a false sense of security, since there is no hard-and-fast genetic link to Alzheimer’s for most people.
  • If you learn you do have the altered gene, you may experience anxiety, depression or guilt about the possibility of having passed a risk factor on to your children. You might also be concerned about your insurance coverage or employment.

What other options are there?
If you have concerns about your memory, your doctor may refer you to a neurologist for an evaluation. Memory testing and brain scans can sometimes provide information about whether or not you are at increased risk of developing Alzheimer’s disease or other memory problems.

What’s The Future Hold?

As researchers learn more about the treatment and prevention of Alzheimer’s, genetic testing will become more useful and more widely available. In the future, researchers may identify additional Alzheimer’s-related genes, making genetic testing more informative.


Alzheimer’s Association
Phone: (800) 272-3900

Alzheimer’s Disease Education and Referral Center
Phone: (800) 438-4380

Alzheimer’s Research Forum

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