Alzheimer's and genetics
introduction
Researchers still don't know exactly what causes Alzheimer's disease . But, as they learn and research more, they are discovering the important role that genes play in the devastating course of the disease.
Gardens
All living things are made up of basic units called cells. Cells are so tiny that they can only be seen through a microscope. Most of the millions of cells in the human body have one nucleus that functions as a control center and houses our 46 chromosomes. A chromosome is a stringy structure found in the cell nucleus, which carries hundreds and sometimes thousands of genes. A person inherits a set of 23 genes from each parent. The genetic material found on these 23 chromosomes is called the "human genome." Following various studies, researchers today believe that the human genome consists of about 30,000 genes. Genes supervise all the construction, operation and repair of body systems. For example, genes contain the information that determines the color of our eyes or hair and other traits that we inherit from our parents. Also, thanks to genes, we have two hands that we can use, such as playing the piano.
But genes alone are not all-powerful. Most genes can do very little good if they are not stimulated by other substances. Despite their necessity, genes wait inside the cell nucleus for other substances to come and read their messages. These messages provide the cell with instructions for building proteins.
Proteins are the building blocks of cells. Bones and teeth, muscles and blood, for example, are made from different proteins. They help our bodies grow and stay healthy. A gene provides the code for making a particular protein. Sometimes a genetic change called a mutation can occur that leads to the creation of a defective protein. In addition to a genetic mutation, the environment (the food we eat, the air we breathe, or chemicals we are exposed to) can also affect the creation of proteins by causing interference with the translation of the genetic message. Defective proteins can cause cell dysfunction, disease and death.
Researchers examine genes to learn more about the proteins they make and what the proteins actually do for the body. They have also been able to discover various diseases that are caused when genes function poorly.
The genetics of Alzheimer's disease
Diseases such as cystic fibrosis and Huntington's disease are the result of a single gene disorder. If a person inherits the gene that causes one of these diseases, they are highly likely to develop the disease. In contrast, Alzheimer's disease, which affects older adults, is not caused by a single gene. Mutations in different genes may increase the risk of the disease, in combination with other factors such as high blood pressure.
Alzheimer's disease is classified into two types – familial and sporadic. Familial AD (FAD) is a rare form of the disease and is seen in less than 5% of Alzheimer's patients. FAD cases begin at a relatively young age, before the age of 65. The disease is caused by a mutation in a gene on chromosomes 1, 14 and 21. Even if a person inherits this mutation from only one of their parents, they will almost always develop Alzheimer's disease at an early age. This type of inheritance is called autosomal dominant inheritance. This means that all offspring in a given generation have a 50% chance of developing FAD if one of their parents has the disease.
ApoE and sporadic Alzheimer's disease
Most cases of Alzheimer's disease are sporadic, meaning they have no known cause. Because this type usually develops after the age of 65, it is referred to as late-onset Alzheimer's disease. Sporadic Alzheimer's disease does not follow a specific hereditary pattern; however, in some families, a cluster of cases is seen. Although no specific gene has been identified as the cause of sporadic Alzheimer's disease, genes play a role in some cases of the disease. Researchers have identified an increased risk of developing sporadic Alzheimer's disease associated with the apolipoprotein E (apoE) gene located on chromosome 19. This gene codes for a protein that carries cholesterol in the bloodstream. ApoE comes in several forms: apoE4 (E4), apoE3 (E3), and apoE2 (E2).
We inherit one apoE allele from each parent. It turns out that if you inherit one or two E4 alleles, your risk of developing Alzheimer's disease increases. In other words, having the E4 allele is a risk factor for Alzheimer's disease, but it does not guarantee that you will develop the disease. Some people who have 2 E4 alleles (who are in the highest risk group) do not develop Alzheimer's, while people without the E4 allele do. The E2 allele is rarer and appears to reduce the risk of developing the disease. The E3 allele is the most common in the general population and probably does not play a role in Alzheimer's disease. Therefore, the degree of risk of developing Alzheimer's disease in a particular person cannot be determined by apoE status.
ApoE testing in research and diagnosis
A blood test can tell which apoE alleles a person has. However, because the apoE4 allele is only a risk factor, the blood test will not predict whether a person will develop Alzheimer's disease. Instead of a clear yes or no answer, the answer is "maybe yes, maybe no." Although some people want to know if they will develop Alzheimer's in old age, it is not yet possible to predict this in advance. In fact, researchers believe that there will probably never be a test that is 100% accurate.
In research, the apoE test is used to identify volunteers at higher risk of Alzheimer's disease. In this way, researchers can examine early changes in the brains of some people. This apoE test helps researchers compare the effectiveness of treatments in patients with different apoE alleles. As mentioned, the researchers believe that the apoE test is useful in studying Alzheimer's disease in large groups of people, but does not help determine the risk of the disease in an individual person. Such a test, which predicts the degree of risk in healthy people for Alzheimer's disease, would be useful if an accurate test were developed along with effective ways to treat or prevent the disease.
The only way to diagnose Alzheimer's with absolute certainty today is to examine brain tissue under a microscope and determine the presence of neuritic plaques and neurofibrillary tangles. This is usually done after the person's death. However, today, doctors can diagnose Alzheimer's disease with 90% accuracy using medical diagnostic tools (including medical history, laboratory tests, neuropsychological tests, and brain scans). The diagnostic process also includes ruling out other diseases and disorders that may cause similar symptoms. If no other cause is found, the diagnosis will be "possible" Alzheimer's. Sometimes an apoE test can be performed in combination with other tests to strengthen the suspicion of Alzheimer's disease. Currently, there is no test for a healthy person, without signs of the disease, that will predict whether he or she is likely to develop it. ApoE testing as a predictive tool is not recommended.
Concern for confidentiality
ApoE testing, and indeed all genetic testing, raises ethical, legal, and social questions, only a few of which are currently answered. In general, confidentiality laws protect information collected about ApoE for research purposes. On the other hand, information collected about ApoE and related to a particular individual may not remain confidential when it is included in the medical record. In the future, various employers, insurance companies, and health organizations may have access to this information and as a result discriminate against the individual. For example, the individual's employment or insurance premium will be affected.
Genetic counseling
Sometimes, research volunteers have the opportunity to learn, during genetic counseling, the results of their apoE test. The meaning of the results is complicated.
People who learn from testing that they are at high risk for the disease may experience depression and emotional distress about their future, as the disease cannot yet be prevented or treated. Therefore, it is recommended that genetic testing results be provided as part of genetic counseling. During counseling, families can learn about the genetics of Alzheimer's disease, the tests themselves, and the possible meaning of the results. Because of issues related to privacy, emotions, and medical care, the primary goal of genetic counseling is to help people with Alzheimer's disease and their families explore and cope with the implications of the information.
Additional research suggests that certain yet unidentified genes may increase the risk of Alzheimer's disease in later life. The U.S. National Institute on Aging (NIA) has begun a major initiative focused on discovering additional genetic risk factors for Alzheimer's disease.
* This article was published by The Alzheimer's Disease Education and Referral (ADEAR) Center, which serves the NIA and is funded by the US federal government.