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Alzheimer's Disease

Genetics and Alzheimer's Disease

Alzheimer disease (AD) is a brain disorder that causes dementia. Late onset AD, the most common type, usually occurs in people over the age of 65. Early Onset Familial Alzheimer Disease, which occurs in fewer than 2% of families with AD, is a genetically inherited form of AD in which symptoms occur before age 65.

The risk of developing AD for a person in the general population is about 10%-15%. This means that for every 100 people, about 10-15 of them will develop Alzheimer disease during their lifetime.

Genetics and Late Onset AD

Although the exact cause of AD is not currently known, research has identified several risk factors that can increase a person's risk of developing AD above the 10%-15% general population risk. It is important to remember that having one or more of these risk factors only means that person's risk of developing AD is higher, it does not mean that the person will definitely get AD. The following is a list of risk factors thought to be associated with an increased risk for developing AD:

The ApoE gene

Genes are made up of DNA and are inherited from our parents on structures called chromosomes. We have two copies of every chromosome (except for the sex chromosomes) because we inherit one copy from our mother and one copy from our father. Since genes are found on chromosomes, and we have two copies of each chromosome, we generally have two copies of each gene, including the ApoE gene.

The ApoE gene makes a protein, called APOE. This protein is involved in cholesterol storage, transport, and metabolism in our bodies. We know that the APOE gene comes in three different forms (called alleles). These alleles are; E2, E3, and E4. Since we all have two copies of this gene (remember, we inherited one copy from each of our parents), and since there are three forms that the gene can have, there are six possible combinations of the APOE gene that a person can have.

The allele that is a risk factor for AD is the E4 allele. If a person has one or two copies of the E4 allele, then that person has an increased chance of developing AD.

Why genetic testing for ApoE isn't recommended

There are a number of reasons why genetic testing for the ApoE gene is not currently recommended.

  1. It is not known for certain just how much a person's risk of developing AD goes up when they have one or two copies of the E4 allele.
  2. There are currently no treatments to prevent or cure AD. This means that if people were to find out they were at higher risk, they would not have any medical options for reducing or eliminating their risk.
  3. Even though genetic testing for the ApoE gene is not currently recommended as part of normal clinical care, researchers are conducting studies of using this genetic test, along with genetic counseling, to give people an idea about their risk of developing AD.

Researchers hope to learn more about the risks of developing AD. Researchers also hope to identify other susceptibility genes but that search has proven more challenging than originally expected. Moreover, it is important to recognize that non genetic factors (diet, exercise) can also
 affect risk for AD.

Genetics and Early Onset Familial Alzheimer Disease

Early Onset Familial Alzheimer disease is rare and only accounts for a small percentage of Alzheimer disease cases. This type of AD is inherited in what is called an autosomal dominant manner. This means that someone who has an affected parent has a 50% chance of inheriting the gene mutation that causes early onset familial AD. If the person does inherit the gene mutation, then it is almost (but not absolutely) certain that they will develop AD. In families with this disease:

So far, there have been three different genes identified that, when there is a mutation in them, cause early onset familial AD. It is likely that there are additional genes that can cause Early Onset Familial AD that have not yet been identified. The identified genes are:

Genetic testing to look for mutations in the PSEN1, PSEN2, and APP genes is available for individuals who have a family history of Early Onset AD. Such testing may inform a person whether or not they have inherited a mutation in one of these three genes, but it does NOT provide any information about:

This type of testing will not always be informative for families, however. This is because not all families with Early Onset Familial AD have mutations in one of these three genes (PSEN1, PSEN2, or APP). As mentioned earlier, there are likely to be other genes that can cause Early Onset Familial AD that have not yet been identified. Mutations in these other genes would not be found by looking at PSEN1, PSEN2, or APP.

Genetics Counseling for Early Onset Familial AD

It is important for people who are considering genetic testing for Early Onset Familial AD to have genetic counseling to make sure that they consider all of the possible implications of learning their genetic test results. It is important to think about the impact genetic information could have on a number of factors. The kinds of issues that are discussed during a genetic counseling session include:

If you have questions about your risk for Alzheimer disease, it is important for you to talk to your doctor. He or she might be able to give you the information you need, or they might be able to refer to a specialist, such as a neurologist or a genetic counselor. Below is a list of resources that may be helpful for people who want more information about this topic.

This article was originally authored by Melissa Butson, ScM, CGC, formerly of Case Western Reserve University, reviewed by Peter J. Whitehouse, MD, PhD, Case Western Reserve University, and published on NetWellness with permission.

For more information:

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This article is a NetWellness exclusive.

Last Reviewed: Oct 20, 2010

Douglas W Scharre, MD Douglas W Scharre, MD
Clinical Associate Professor of Neurology
Clinical Associate Professor of Psychiatry
College of Medicine
The Ohio State University