Genes in Late-onset Disease
The majority of AD cases are late-onset, usually developing after age 65. Late-onset AD has no known cause and shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. Although a specific gene has not been identified as the cause of late-onset AD, genetic factors do appear to play a role in the development of this form of AD. Only one risk factor gene has been identified so far.
Researchers have identified an increased risk of developing late-onset AD related to the apolipoprotein E gene found on chromosome 19. This gene codes for a protein that helps carry cholesterol in the bloodstream. The APOE gene comes in several different forms, or alleles, but three occur most frequently: APOE e2, APOE e3, and APOE e4.
People inherit one APOE allele from each parent. Having one or two copies of the e4 allele increases a person's risk of getting AD. That is, having the e4 allele is a risk factor for AD, but it does not mean that AD is certain. Some people with two copies of the e4 allele (the highest risk group) do not develop clinical signs of Alzheimer's disease, while others with no e4s do. The e3 allele is the most common form found in the general population and may play a neutral role in AD. The rarer e2 allele appears to be associated with a lower risk of AD. The exact degree of risk of AD for any given person cannot be determined based on APOE status. Therefore, the APOE e4 gene is called a risk factor gene for late-onset AD.
Scientists are looking for genetic risk factors for late-onset AD on other chromosomes as well. They think that additional risk factor genes may lie on regions of chromosomes 9, 10, and 12.
The National Institute on Aging (NIA) has launched a major study to discover remaining genetic risk factors for late-onset AD. Geneticists from the NIA's Alzheimer's Disease Centers are working to collect genetic samples from families affected by multiple cases of late-onset AD. Researchers are seeking large families with two or more living relatives with late-onset AD. Families interested in participating in this study can contact the National Cell Repository for Alzheimer's Disease at 1-800-526-2839. Information may also be requested through their website, http://ncrad.iu.edu.
ApoE Testing in Research or Diagnosis
A blood test is available that can identify which APOE alleles a person has. However, because the APOE e4 gene is only a risk factor for AD, this blood test cannot tell whether a person will develop AD or not. Instead of a yes or no answer, the best information a person can get from this genetic test for APOE is maybe or maybe not. Although some people want to know whether they will get AD later in life, this type of prediction is not yet possible. In fact, some researchers believe that screening measures may never be able to predict AD with 100 percent accuracy.
In a research setting, APOE testing may be used to identify study volunteers who may be at a higher risk of getting AD. In this way, researchers can look for early brain changes in some patients. This test also helps researchers compare the effectiveness of treatments for patients with different APOE profiles. Most researchers believe that the APOE test is useful for studying AD risk in large groups of people but not for determining one person's individual risk. Predictive screening in otherwise healthy people will be useful if an accurate/reliable test is developed and effective ways to treat or prevent AD are available.
In diagnosing AD, APOE testing is not a common practice. The only definite way to diagnose AD is by viewing a sample of a person's brain tissue under a microscope to determine if there are plaques and tangles present. This is usually done after the person dies. However, through a complete medical evaluation (including a medical history, laboratory tests, neuropsychological tests, and brain scans), well-trained doctors can diagnose AD correctly up to 90 percent of the time. Doctors look to rule out other diseases and disorders that can cause the same symptoms of AD. If no other cause is identified, a person is said to have "probable" or "possible" AD. In some cases, APOE testing may be used in combination with these other medical tests to strengthen the diagnosis of a suspected case of AD. Currently, there is no medical test to establish if a person without the symptoms of AD is going to develop the disease. APOE testing as a patient screening (predictive) method is not recommended.