Using the APOE4 Gene to Determine Alzheimer's Care

Richard S. Isaacson, MD


December 11, 2018

Hello. I'm Dr Richard Isaacson, director of the Alzheimer's Prevention Clinic at Weill Cornell Medicine and NewYork-Presbyterian in New York City.

Is it time to start using the apolipoprotein ε4 (APOE4) gene tests to better inform our clinical practice? A new review paper[1] in the Journal of the Prevention of Alzheimer's Disease, by Berkowitz, [myself], and colleagues, talks about how the presence or lack of the APOE4 gene may help to better personalize or guide risk-reduction care for Alzheimer's disease. This field is complicated, which is why this paper is so useful for establishing what the data show.

Studies such as the FINGER trial[2] have shown that a multimodal lifestyle intervention including exercise, nutrition, and cognitive stimulation, in addition to regular follow-up visits with a treating physician or nurse practitioner, can actually have robust effects regardless of whether you have the APOE4 gene or not.

However, the question remains as to whether knowledge is power when it comes to knowing whether a person does have the APOE4 gene. I do think this is the case, not just for the physician but potentially also for the patient. For example, research has shown that physical activity may be even more important when looked at in isolation for people with the APOE4 gene.[3] Sedentary people with the APOE4 gene have higher amyloid levels in the brain.[4] When it comes to nutrition, one study actually showed that the Mediterranean-style diet works preferentially well for people who do not have the APOE4 gene.[5]

If someone has the APOE4 gene, we do know that they better stop smoking tobacco, because there is a specific interaction noted there.[6] This highlights the role of epigenetics, the environmental interaction with genes to increase or decrease your risk for a disease. Tobacco plus the APOE4 gene presses the fast-forward button towards Alzheimer's disease.

There were a variety of other studies that showed that people with two copies of the APOE4 gene should possibly start thinking about what their vitamin D level is.[7] Having an elevated vitamin D level—[or even high-normal] to, say, 50 to 70 in one study—actually may be even more protective for people with two copies of the APOE4 gene.

There is also the question of the role of vitamins and supplements. Although the initial study[8] for people with mild to moderate Alzheimer's disease showed no effect when looking at supplementation with omega-3 fatty acids, recent studies[9] have actually shown that people with the APOE4 gene may respond preferentially to omega-3 fatty acid supplementation. However, the key here is that it takes 2.5 years for the amount of omega-3s to really replenish the brain.[10] So a person may need to ensure that they're getting omega-3s in their diet or from supplements for a long period of time, especially if they have the APOE4 gene. That may differ for a variety of other interventions, depending on whether you have or do not have the APOE4 gene.

In an effort to better personalize your patients' care, I recommend that you check out this new paper. Thank you very much.


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