Genetics and Alzheimer's Disease
Is AD inherited? Rarely. The genetic or "inherited" type of AD (also referred to as "familial" AD) accounts for only 1-5% of all cases of AD. People with the inherited form of AD are born with specific genetic mutations on either Chromosome 1, 14, or 21. Essentially, these individuals are born with the disease, and if they live long enough, they will develop AD. Typically, these individuals will develop AD before the age of 65. To date, there are only about 200 families known worldwide who carry the chromosomal mutations which cause this form of AD. Therefore, to have the inherited form of AD, you must be a descendant of one of these families.
The remaining 95-99% of AD cases are not genetically transmitted, and it is not known what causes this form of the disease. The risk of developing the non-inherited form of AD (also called “sporadic” AD) increases significantly with age. By age 65, the lifetime risk for developing AD is approximately 12%. By age 75, the risk doubles to 24%. By age 85, the lifetime risk for developing AD is roughly 47%. In other words, if everyone sitting in the room with you lived to age 85, almost half would develop AD. Aging, not genetic heritability, is the primary risk factor for developing AD.
Researchers have identified a genetic risk factor which may increase a person's risk for developing AD. That risk factor is the Apolipoprotein E(ApoE) gene, which is located on chromosome 19. This gene is involved in determining what type of cholesterol carrying protein is inherited. There are three different forms of the ApoE gene (ApoE 2, ApoE 3, and ApoE 4). Each person inherits either a 2, 3, or 4 version of the gene from each parent, so that all people end up with either a 2/2, 2/3, 2/4 combination, a 3/3 or 3/4 combination, or a 4/4 combination.
Research indicates that inheriting an ApoE 2 version of the gene may help protect against developing AD, or perhaps delay the onset of the disease. The ApoE 3 gene is neutral and neither increases nor decreases risk for AD. Inheriting a type 4 version of the ApoE gene increases one's risk for developing AD. However, only about half of all patients with AD have a type 4 version of the gene, and among all persons who do inherit an ApoE 4 gene, only a subset will develop AD. Clearly, inheriting an ApoE 4 gene does increase risk for developing AD, but it does not cause AD.
It is important to keep in mind that inheriting the disease is not the same thing as inheriting a risk factor for the disease. Many risk factors for AD have been identified The ApoE gene is only one of those risk factors.
The issue of genetic testing for AD is often raised by family members of patients. Pursuing testing to determine if you have inherited an AD gene is not advised except under special circumstances. Genetic testing may be appropriate for family members who are descendants of one of the 200 known AD families, or for persons with an extensive family history of AD (multiple family members across multiple generations with onset at a young age) of AD. In these cases, genetic counseling should occur in conjunction with chromosomal testing. For family members of persons with the non-inherited form of AD (sporadic AD), genetic testing should not be performed. Family members are also strongly discouraged from seeking ApoE testing to determine whether this risk factor has been inherited. Why? First, the test has no predictive value and cannot determine whether AD will develop. Second, should you pursue testing and learn that you have inherited the ApoE risk factor for AD, it is possible that you would be viewed as having a greater risk for developing AD by insurance companies, including those providing long term care policies. Lastly, knowing that you carry a risk factor does not protect you from developing AD, and, in fact, may have a negative impact on your psychological or emotional well being.