by Julie Simon, MS, CGC
In the new mini-series Limitless, Chris Hemsworth sets out to explore ways to combat aging and live a long and healthy life. It will come as no surprise to most that the answer lies in being active, eating well, and spending time with your friends and family. Sure, there are some other great tips included like cold water exposure therapy and meeting with a death doula, but the real surprise came in episode 5. While meeting again with the longevity physician Dr. Attia, Chris Hemsworth learns that he carries two copies of the APOE e4 gene variant. This increases the chance that he will develop Alzheimer’s disease later in life.
What do the genetic results mean?
Among other blood tests, Chris Hemsworth received results for the APOE gene, which codes for the protein apolipoprotein E. This gene is important for cholesterol metabolism in the body and one of the most frequently studied genes related to Alzheimer’s disease risk. Alzheimer’s disease is a neurodegenerative disease that causes dementia. We all have two copies of this gene and there are three common versions (aka “alleles”) of the APOE gene known as e2, e3, and e4.
First, let’s be clear about what the results are not saying: these genetic test results do not diagnose Alzheimer’s disease and they do not mean he will definitely develop Alzheimer’s disease in the future. The average American has about a 1 in 10 or 10-12% chance of developing Alzheimer’s disease, and most cases won’t be diagnosed until age 60 or later. A small percentage of people will develop symptoms before age 60, but early onset Alzheimer’s disease is not associated with the APOE gene. Most people with Alzheimer’s disease have no known genetic cause.
People with two copies of the APOE e4 allele, like Chris Hemsworth, have a 25-35% chance of developing Alzheimer’s disease by the age of 75. This is the same chance of developing Alzheimer’s disease that one would have simply from having a first-degree relative (i.e. a parent or sibling) affected with Alzheimer’s disease. There is more information about the genetics of Alzheimer’s disease in a previous blog here. These results are a risk factor, one of many possible risk factors in someone’s life, that can affect how likely (or unlikely) it is for someone to develop Alzheimer’s disease. There are other risk factors, such as other genes that play a role in how likely you are to develop Alzheimer’s disease as well as when people may start to show symptoms.
What do the results mean for family members?
Each of us inherits two copies of the APOE gene, one from each biological parent. Given his results, we would assume he inherited one e4 copy from each parent. Generally, about 25% of the population would be a carrier of one copy of the APOE e4 allele, while 2-3% of the population have two copies like Chris Hemsworth. Like many of us his next question is “What does this mean for my family and my children?”.
His siblings, namely Luke and Liam Hemsworth, have an increased chance of having the same results as Chris, but their exact risk depends on their parents’ APOE status. The specifics can get pretty complicated, but a Genetic Counselor can walk you through them, help explain what it means, what the potential results are for you, and why we differentiate the common variants.
Since these results do not change any healthcare recommendations for children, testing is not recommended in minors. Once children are adults, they can decide for themselves whether they want to learn this type of information. As we can see from Chris’s experience, an increased risk of any size can have a big impact on our life choices, which is one of the reasons we avoid testing for adult-onset conditions in minors. This may be a little more controversial, but testing is not necessarily recommended for his brothers, since these results do not change the healthcare recommendations for an adult either. If his brothers do decide to pursue testing, I certainly hope they will explore the implications of this testing with a Genetic Counselor first!
Genetic Counseling for Alzheimer’s Disease
Discussions about Chris’s genetic test results and Alzheimer’s disease are brief and sprinkled throughout the episode of “Limitless.” This helps build intrigue for the episode but is a far cry from the level of discussion these results really need. Ideally, Chris would have also been shown meeting with a genetic counselor, who could explore information about the genetic test, potential results, the benefits and limitations, emotional, familial, and medical implications, and answer any questions before, during, and after testing. Now that would be a great episode!
From reading further about his specific case, including the interview he conducted with Vanity Fair, there really was more going on behind the scenes (thank goodness!). It was a pleasant surprise to see the mention that the ordering doctor did call Chris Hemsworth to discuss the results prior to filming and gave him the option to not film this section. From a genetic counselor’s perspective, it is important for a person to be able to have a safe space to process the results of genetic testing and be able to ask follow up questions. Ideally, someone familiar with the potential benefits and limitations of this testing would meet with you before and after testing is completed.
A genetic counseling appointment for Alzheimer’s disease would start with a review of your personal health and family history, which allows the genetic counselor to provide a more personalized assessment of your risk. As the episode progressed, we learned that Chris Hemsworth’s grandfather had Alzheimer’s disease, so Chris already had some familiarity with the disease and was aware of the limited options to prevent or slow progression of symptoms . The absence of a cure is not necessarily a reason to avoid testing, although it is certainly a reason to be fully informed before pursuing testing. For some people, like Chris, knowledge is power, and genetic testing results like this can allow people to make some positive choices in their life and overall health (which goes to the heart of this documentary). I think Chris Hemsworth beautifully discusses these changes in the Vanity Fair article, opting to be more choosy in his career, spending more time at home with his wife and child, and being able to shift the balance in his life.
There are many topics that may be covered in an individual’s genetic counseling session. Ideally, genetic testing would be started in a family member who has been diagnosed with the condition in question (like Chris’s grandfather). The concerns around “proactive” testing (meaning testing in an unaffected individual to more accurately define risks) are different from those that arise when testing an individual who already carries a diagnosis. It could be that his grandfather with Alzheimer’s also has two e4 variants, or none. This is only one factor in Alzheimer’s risk. With proactive testing, we worry about uninformative negative results. This happens when a patient has negative genetic testing results but in reality still has an elevated risk of developing the disease, such as negative APOE testing when a person has a family history of the condition. A negative genetic testing result in this case would not remove the increased chance of developing Alzheimer’s disease. This makes it difficult to fully interpret the results or predict all of those who will go on to develop Alzheimer’s disease later in life.
Finally, they can discuss the implications of genetic testing for family members. Genetic testing results often reveal the genetic status of relatives (i.e. we now know his parents each carry at least one e4 allele for APOE) and so even if family members did not consent to testing, sometimes genetic testing may reveal risks for them as well. The question was raised in the show and resulting interviews, but there was not a great answer. To be fair, this may be because it is a nuanced situation or out of respect for the family’s privacy, but there are no obvious ways to tell what a person’s results are from just looking at them, or can be assumed from looking at the family tree. It could be that his grandfather with Alzheimer’s also has two e4 variants, or none. This is only one factor in Alzheimer’s risk.
Other lessons learned from Limitless
Chris Hemsworth is continuing his lessons learned from the show. He recently shared that one of the people he met while filming the show is not doing well. Natalie Fornasier is the young patient with advanced melanoma (a particular type of skin cancer) in episode 6 who shares her story. She’s been an outspoken advocate of awareness, screening, and prevention options for melanoma in the 8 years since her initial diagnosis. He kept in touch with her and shared her story in the hopes of continuing to spread her message of living life to the fullest and prioritizing people and relationships.
Keeping hope in the face of adversity is challenging, especially with the many heavy topics that we address in genetic counseling. Maybe you’d rather walk away and not know your APOE status at this time. Maybe just the conversation is enough to inspire changes in your life. Maybe you’d be reassured knowing you don’t have two copies of the e4 variant, or maybe learning you carry an increased risk allows you to join support organizations and get involved with research opportunities. Maybe your kids are pestering you for testing and you’d like to get good information to share with them to better address their questions and concerns.
The response to Limitless on social media was overwhelmingly positive. He had access to all the best and brightest experts in their respective fields, which makes for a sensational and hopefully inspiring documentary. I appreciate his willingness and insistence that his results be included in the final cut. It has started a conversation.
Here at Genetic Support Foundation, we prioritize independent genetic counseling that is free from industry influence. This means that you, the patient, having access to unbiased and accurate information is our top priority – whether or not you decide to have genetic testing done. Financial assistance and insurance billing options are available. If you have questions about Alzheimer’s disease and your family information, consider scheduling an appointment with one of our board certified genetic counselors.