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Should You Check Your Genes for Alzheimer’s Disease?

Here’s what you need to know about genetic risk factors for Alzheimer’s.

The FDA now allows direct-to-consumer genetic tests that include the APOE gene, the most common risk factor for Alzheimer’s disease. You might wonder why we doctors don’t order this test in routine clinical practice.

First, a little background information:

  • There are three common types of the APOE gene, e2, e3, and e4. Because we inherit one copy from our mother and one from our father, there are six possible combinations (order doesn’t matter): e2/e2, e2/e3, e2/e4, e3/e3, e3/e4, and e4/e4.
  • About 70% of people have one or two copies of the APOE e3 gene. Because this is the most common type, e3/e3 provides the baseline risk of Alzheimer’s.
  • About 5-10% of people have one or two copies of the APOE e2 gene. Compared to having e3/e3, those who have e2/e3 or e2/e2 have a lower risk of Alzheimer’s.
  • Some people, about 10-15%, have one or two copies of the APOE e4 gene. Compared to having e3/e3, those who have e2/e4, e3/e4, or e4/e4 have a higher risk of Alzheimer’s, and generally develop it at a younger age.
    • One study found that, compared to e3/e3, the odds of developing Alzheimer’s was about 3 times more likely if one has e2/e4, 4 times more likely if one has e3/e4, and 12 times more likely if one has e4/e4.
    • Compared to the average age of the onset of Alzheimer’s at 78.4 years without an e4 gene, those with one e4 gene who developed Alzheimer’s did so around age 75.3, and those with e4/e4 developed Alzheimer’s around age 72.9 (Sando et al., 2008).
  • One study found that, compared to e3/e3, the odds of developing Alzheimer’s was about 3 times more likely if one has e2/e4, 4 times more likely if one has e3/e4, and 12 times more likely if one has e4/e4.
  • Compared to the average age of the onset of Alzheimer’s at 78.4 years without an e4 gene, those with one e4 gene who developed Alzheimer’s did so around age 75.3, and those with e4/e4 developed Alzheimer’s around age 72.9 (Sando et al., 2008).

Here are the reasons why we don’t routinely order an APOE genetic test on our patients:

  • Having an e4 gene is not necessary to develop Alzheimer’s. About half of patients with Alzheimer’s do have an e4 gene—but the other half do not! Thus, one should not think, “Oh, I don’t have an e4 gene so I won’t get Alzheimer’s,” that’s just not correct.
  • Having an e4 gene does not mean that one will develop Alzheimer’s. There are many people with one or two e4 genes who live over 100 years without Alzheimer’s. In fact, in individuals above age 90, an e4 gene does not increase the risk of developing Alzheimer’s (Corrada et al., 2013).
  • It is important to keep a positive mental attitude toward aging and life in general. Some individuals have difficulty keeping a positive attitude when told their APOE genotype.
  • Because genes are present from birth, APOE genotyping cannot be used to distinguish mild Alzheimer’s from normal aging.
  • Engaging in at least 30 minutes of aerobic exercise each day and following the Mediterranean diet will lower one’s risk of Alzheimer’s disease—regardless of one’s APOE genes (e.g., Head et al., 2012).
  • Although we currently have good medications to treat the symptoms of Alzheimer’s, we have no treatments to stop it from developing. (Note that when we do have treatments to stop Alzheimer’s disease from developing, everything will change, including my advice on this topic.)

So why would you want to know your APOE genotype? Although I’m not convinced there is a good reason to know, here are a few possible arguments as to why people might want to:

  • You want to take that big trip on your 75th birthday, and you’d like to make sure you’ll remember it.
    • As mentioned above, the average age of developing Alzheimer’s disease varies depending upon whether one has 0, 1, or 2 APOE e4 genes. So, if you have an e4 or two, perhaps it would better to take that trip at a younger age.
    • On the other hand, if that trip is important to you, you should take it sooner rather than later anyhow—there are other diseases besides Alzheimer’s that could cause a physical or mental disability.
  • You’re planning for retirement and you need to figure out how many years of life you need to save for.
    • Because with one or two e4 genes you’re more likely to develop Alzheimer’s at a younger age, in theory, you might not need to save as much as you would if you didn’t have an e4.
    • On the other hand, there are many people with APOE e4/e4 who live into their 90s.
  • As mentioned above, the average age of developing Alzheimer’s disease varies depending upon whether one has 0, 1, or 2 APOE e4 genes. So, if you have an e4 or two, perhaps it would better to take that trip at a younger age.
  • On the other hand, if that trip is important to you, you should take it sooner rather than later anyhow—there are other diseases besides Alzheimer’s that could cause a physical or mental disability.
  • Because with one or two e4 genes you’re more likely to develop Alzheimer’s at a younger age, in theory, you might not need to save as much as you would if you didn’t have an e4.
  • On the other hand, there are many people with APOE e4/e4 who live into their 90s.

Regardless of our genes, we’re all at risk for Alzheimer’s. I recommend that everyone engage in aerobic exercise, follow the Mediterranean diet, and keep medical illnesses like hypertension, heart disease, increased cholesterol, and diabetes under good control.

© Andrew E. Budson, MD, 2017, all rights reserved.

References

Sigrid B Sando Stacey Melquist, Ashley Cannon, Michael L Hutton, Olav Sletvold, Ingvild Saltvedt, Linda R White, Stian Lydersen and Jan O Aasly. (2008) APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; A case control study from central Norway. BMC Neurology 8:9. https://doi.org/10.1186/1471-2377-8-9

Corrada, M. M., Paganini-Hill, A., Berlau, D. J., & Kawas, C. H. (2013). APOE genotype, dementia and mortality in the oldest-old: The 90+ Study. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 9(1), 12–18. http://doi.org/10.1016/j.jalz.2011.12.004

Head, D., Bugg, J. M., Goate, A. M., Fagan, A. M., Mintun, M. A., Benzinger, T., … Morris, J. C. (2012). Exercise engagement as a moderator of APOE effects on amyloid deposition. Archives of Neurology, 69(5), 636–643. http://doi.org/10.1001/archneurol.2011.845

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