APOE4 Is A Genetic Risk Factor For Alzheimer's — Should You Find Out Your Status?
Chris Hemsworth is literally the picture of health and fitness. But no one is invincible. And as he was truly testing the boundaries of the human body and mind in his 2022 National Geographic docuseries Limitless With Chris Hemsworth he found out that he has two copies of the APOE4 gene—putting him at an increased risk for developing Alzheimer's disease—from a consultation with longevity-focused doctor Peter Attia, M.D.
Completing this genetic test may seem like something only available to the elite or through specialty doctors, but it's actually included in many direct-to-consumer DNA kits.
But is this test actually beneficial? That is a hard-hitting question that physicians and researchers go back and forth on.
That's because, on one hand, the APOE4 variant doesn't predict your risk of Alzheimer's disease—you may get Alzheimer's with or without having a genetic risk for it. On the other hand, lifestyle plays an outsized role in the development of Alzheimer's—so much so that it may balance out the likelihood of Alzheimer's disease regardless of genetic risk.
At mindbodygreen, we're proponents of taking a proactive approach to your health by harnessing the power of data that's available to you—if you want to use it.
So to help you make an informed decision on whether or not to find out your risk, we're going to dive into the nitty-gritty behind what this genetic risk even means, share clinician perspectives, and dissect the correlation between lifestyle habits and Alzheimer's risk.
What is APOE4?
APOE is a gene that provides the body with instructions for making a protein called apolipoprotein E (typically involved in the metabolism of fats in the body).
There are several versions of the APOE gene and APOE4 is the one that's linked to increasing a person's risk for developing late-onset (aka after age 65) Alzheimer's disease—the most common form of dementia that affects over 6.7 million Americans.
You can inherit an APOE4 gene from each parent. About 25% of people carry one copy of APOE4, and only about 2-3% of people carry two copies. Chris Hemsworth falls into the latter, which Attia discerned during the series may put him at an eight to 10 times higher risk of developing Alzheimer's
And while this association is well established, we still don't know exactly how APOE4 influences Alzheimer's risk. This chronic condition is characterized by the buildup of amyloid plaques (clumps of protein), tangled bundles of fibers, and the loss of connection of neurons. Some research shows that having an APOE4 gene is linked to having more amyloid plaques.
The limitations of APOE4 testing
Integrative neurologist Romie Mushtaq, M.D., notes that genetic tests are not routinely used in clinical settings—even integrative ones—to diagnose or predict the risk of developing Alzheimer's or related dementia.
"Although APOE testing is also available, the results cannot fully predict who will or won't develop Alzheimer's," she notes. Even if you have one or both copies of the APOE4 gene, it doesn't mean that you will develop Alzheimer's, and not everyone with Alzheimer's has a copy of APOE4.
The Alzheimer's Association also emphasizes the relationship between APOE4 and Alzheimer's is the strongest in white, European-descended populations. And according to new research, that association is not as well established for other populations.
"I want to honor that watching a loved one suffer through dementia of any type is heartbreaking and traumatic," says Mushtaq. "I have experienced this both as a neurologist taking care of patients with memory loss, and by watching my beloved maternal grandmother suffer from dementia. Unfortunately, genetic testing is not the end-all and be-all answer."
But some clinicians like Attia and precision medicine physician Matt Dawson, M.D., are recommending folks learn the APOE4 status to identify any genetic disadvantage they may have to work harder to overcome.
APOE4 insights may help motivate behavior change
"Women are advised if their family history is suggestive of breast cancer to make sure they don't have breast cancer genes. Why? Because they can act on that information and prevent breast cancer," Attia said on a mindbodygreen podcast. "Knowing that you have an APOE4 gene will allow you to do a lot of things to mitigate the risk of dementia."
And Mushtaq does agree that we are more in control of our long-term brain health than we realize. "Most Alzheimer's disease cases have to do with lifestyle and health choices regarding our nutrition, movement, sleep routines, meditation, and social connections we make starting in our 30s and beyond."
While everyone can benefit from brain-protecting habits, it may be especially important for those who have an APOE4 gene. A 2019 study published in JAMA found that making favorable lifestyle choices was linked to a lower risk of dementia1—regardless of genetic risk. Whereas following unfavorable habits and having a high genetic risk significantly increased dementia risk.
Attia even told Hemsworth during the Limitless series that his test result was a blessing. "This will motivate you to take steps today that most people [in their 40s] would never think about until they're in their 50s or 60s," he said.
Dawson mentioned on mindbodygreen's podcast that his mom has APOE4, so they're going to focus on a few different things for her that we wouldn't if she didn't have that gene.
Lifestyle changes to help reduce your risk of dementia
None of these habits are revolutionary or deviate far from the path of what's considered generally healthy. "It's the things that we all know, but they're that much more important to optimize when it comes to brain health," Dawson previously told us.
- Sleep: Sleep plays such an underrated yet crucial role in every major body system. And Attia emphasized on the podcast that optimizing your sleep is one of the most important things you can do if you're at risk of dementia. Improving your sleep means setting a consistent sleep/wake schedule, keeping your bedroom cool and dark, and even trying a sleep supplement.
- Exercise: Both Attia and Dawson stress the importance of exercise when it comes to dementia prevention. High-intensity exercise is especially beneficial as it triggers an increase of BDNF2 in your brain. BDNF stands for brain-derived neurotrophic factor2, which is a protein that improves memory, learning, and complex thinking by stimulating neurons. As Dawson puts it, "[It's] basically like Miracle-Gro for your brain."
- Focus on metabolic health: Metabolic health and brain health are closely intertwined. Mushtaq also mentioned that the presence of APOE4 is also a known factor for insulin resistance. Insulin is the hormone that helps the body lower blood sugar levels and utilize glucose. Elevated blood insulin levels3 are believed to precede Type 2 diabetes by 10 to 15 years. Poorly controlled blood sugar levels increase the risk of Alzheimer's disease, which is now sometimes referred to as Type 3 diabetes. So focusing on blood sugar control like eating more fiber and protein at meals (along with complex carbohydrates) and exercising is beneficial.
- Drink less alcohol: A study published in 2023 that analyzed data from almost four million people in Korea4 found that maintaining mild to moderate alcohol consumption and reducing alcohol intake from heavy to moderate reduced the risk of developing Alzheimer's disease. (Moderate drinking5 is considered one drink a day for women and two a day for men). So you don't necessarily have to quit drinking altogether but rather be more mindful and picky when you do drink.
- Decrease inflammation: Attia also emphasized the importance of lowering inflammation to help protect against Alzheimer's disease. This includes limiting (or avoiding) inflammatory foods and eating more antioxidants (like lutein and zeaxanthin).
So, should you find out whether you have APOE4?
Many people may be hesitant to undergo genetic testing, as they fear a futile outcome—which is valid.
But your daily habits in pretty much every decade can sway whether or not you develop Alzheimer's. Finding out your genetic risk of Alzheimer's can shed light on just how important a healthy lifestyle is for your brain health—especially if you have two copies of the gene—and how detrimental unhealthy habits are for further raising your risk for Alzheimer's.
As Hemsworth said on his show, "The idea that I won't get to remember the life I've experienced, or my wife, my kids… this is probably my biggest fear." Knowing his genetic risk for Alzheimer's has shaped the way he'll live his life moving forward.
However, as lifestyle appears to be a main driving factor of Alzheimer's, making healthy choices, regardless of knowing your genetic risk, is most important.
Personally, as a 28-year-old dietitian with no family history of Alzheimer's, I have not and am not urgently seeking a genetic test to capture my APOE4 status. I'm not against knowing (and will honestly likely get a test at some point in my life), but I'm confident that the lifestyle choices I'm currently making align with what is best for my future brain health, and knowing these results won't really shift my daily decisions.
There are a lot of varying views when it comes to this testing. The most important one, though, is your own.
The mindbodygreen POV
Having the APOE4 gene indicates that you may be at an increased risk of developing Alzheimer's disease later in life—but your genes aren't your destiny.
Whether or not you decide to go through with genetic testing for APOE4 (or you found the result unknowingly from say a 23andMe test) is completely your decision. Some people prefer not to know because it may incite fear, and it's still not an indicator of whether you will develop the disease or not. But having test results can provide a sense of relief from uncertainty and help you make informed decisions about health moving forward.
Molly Knudsen, M.S., RDN is a Registered Dietician Nutritionist and mindbodygreen's supplements editor. She holds a bachelor’s degree in nutrition from Texas Christian University and a master’s in nutrition interventions, communication, and behavior change from Tufts University. She lives in Boston, Massachusetts and enjoys connecting people to the food they eat and how it influences health and wellbeing.