Derek Burnett
Derek Burnett is a Contributing Writer at Bottom Line Personal, where he writes frequently on health and wellness. He is also a contributing editor with Reader’s Digest magazine.
Alzheimer’s is a complex disease driven by many different factors, some of them modifiable (such as diet and exercise) and others non-modifiable. Genetic makeup is a non-modifiable risk factor. So, then, is Alzheimer’s hereditary? The answer is that while genetics will play a role in a person’s risk for developing Alzheimer’s, it usually isn’t the sole determinant of whether we’ll get the disease. Nearly all cases of Alzheimer’s are known as “sporadic” disease because they depend on the interplay of numerous risk factors, just one of which is genetics.
Alzheimer’s is a complex disease driven by many different factors, some of them modifiable (such as diet and exercise) and others non-modifiable. Genetic makeup is a non-modifiable risk factor. So, then, is Alzheimer’s hereditary? The answer is that while genetics will play a role in a person’s risk for developing Alzheimer’s, it usually isn’t the sole determinant of whether we’ll get the disease. Nearly all cases of Alzheimer’s are known as “sporadic” disease because they depend on the interplay of numerous risk factors, just one of which is genetics.
Family history is important when it comes to assessing Alzheimer’s risk. We know, for example, that having a parent or sibling with Alzheimer’s doubles a person’s risk of developing the disease. Clearly, the absence or presence of specific genes has a great deal to do with Alzheimer’s risk, but it’s important to remember that a person’s genetic makeup could possibly decrease their risk for Alzheimer’s.
As we mentioned earlier, genetic risk for Alzheimer’s most strongly centers on a gene that controls production of the apolipoprotein E (ApoE) protein, which breaks down fats in the body. Every human receives two ApoE alleles (subtypes), one from each parent. The three possible ApoE subtypes are ApoE2, ApoE3, and ApoE4. So, for example, an individual could receive an ApoE2 allele from their father and an ApoE4 allele from their mother. Another could receive two ApoE2 alleles, one from each parent. A third individual could receive an ApoE3 allele from their father and an ApoE4 allele from their mother.
Which of those alleles an individual inherits can have a strong impact on their risk of developing Alzheimer’s, since each of the three alleles is associated with different outcomes:
For most people, it’s theoretically possible to have a high-risk genetic makeup yet still not develop Alzheimer’s disease unless other factors happen to be in place. But an unlucky few (about 1% of all Alzheimer’s cases) have genetic abnormalities that make Alzheimer’s an inevitability. With dreadful certainty, Alzheimer’s strikes these adults typically before they turn 51. Such people are said to have “familial” or “genetically determined” Alzheimer’s, and they have a 50% chance of passing the faulty genes on to their children.
There are three genes implicated in familial Alzheimer’s, and all three have to do with beta-amyloid and the production of plaques in the brain. One of those three genes, when defective, produces abnormal APP, which breaks down into beta-amyloid. Mutations of the second and third genes result in the presence of two proteins called presenilin 1 and presenilin 2, which drive the process whereby APP gets broken down into beta-amyloid. While it’s possible to have defects of two or even all three of these genes, a mutation on only one is necessary to trigger familial Alzheimer’s. Researchers are studying adults with familial Alzheimer’s, both to learn more about the disease and to discover possible therapies for slowing or preventing its onset.
Researchers are working on new techniques to modify people’s DNA and manipulate the genetic factors behind Alzheimer’s disease. Targeting brain cells, researchers introduce new genes or replace or remove existing ones, resulting in the production of beneficial molecules that, for example, remove amyloid plaque. Unfortunately, such efforts are still very much in the experimental stage. Although animal studies have shown some promise, it may still be years before safe and effective gene therapies are available for humans.
Genetic testing is usually done through a doctor during the process of diagnosing Alzheimer’s. If you have good reason to believe you’ve inherited familial Alzheimer’s, you should talk to your doctor about testing. But if you have no family history of Alzheimer’s and are just curious, proceed with caution.
It’s possible, for example, to learn whether you carry the ApoE4 allele by using a popular at-home genetic testing kit. But before doing the test, ask yourself what you would do with the information if the results indicated that you carry the allele. It certainly should not be taken as a diagnosis of Alzheimer’s, nor would it mean that you are destined to develop the disease. Presumably, you’d want to look to your modifiable risk factors either way, since someone with or without the allele can get Alzheimer’s. Knowing that you have the ApoE4 allele could cause you years of stress…and anxiety is a risk factor for Alzheimer’s. In any event, if you opt for genetic testing, be sure to involve your doctor in the process so that he or she can help you interpret the results and their implications.
