Last month, Chris Hemsworth announced that he would be taking a break from acting after learning that he has a genetic variant that increases his risk of developing Alzheimer’s disease. The revelation, which came via a genetic test conducted for the docuseries. UnlimitedIt wasn’t entirely surprising, Hemsworth said. vanity fair: Your grandfather has Alzheimer’s, and the condition is highly heritable.
The news was a shock, no doubt. But that doesn’t mean Hemsworth’s future is predicted, according to experts. In fact, his experience is one reason experts say he may want to avoid getting tested for this particular variant, even though testing is an option with some mail-order genetic tests.
For one, the tests can only identify risk, not predict who will actually develop Alzheimer’s disease. Conversely, many people who develop the disease do not have this genetic variant or allele.
The gene, known as APOE-e4, is considered a risk factor but not a cause of the disease.
“We know that people who have APOE-e4 [can] live a long life without developing Alzheimer’s disease,” said Dr. Richard Mayeux, chair of the department of neurology at Columbia University’s Vagelos College of Physicians and Surgeons.
While lifestyle changes such as exercise can help, there are few effective ways to slow or delay Alzheimer’s disease.
“I don’t recommend genetic testing for Alzheimer’s, because if I find out that you have a mutation, there’s nothing I can do to prevent you from getting Alzheimer’s,” Mayeux said, though “that may change.”
What causes Alzheimer’s disease?
Alzheimer’s is the most common form of dementia, affecting an estimated 6.5 million Americans, most of them age 65 or older. That number is likely to double by 2050, according to the Alzheimer’s Association. Experts are still investigating the causes, but it is clear that both genes and environmental factors play a role.
“It’s a polygenic disorder, which means there are many genes that can affect the development of Alzheimer’s disease,” said Dr. Douglas Scharre, director of the Division of Cognitive Neurology at The Ohio State University Wexner Medical Center. “Lifestyle factors may separately influence the development of Alzheimer’s disease. Some conditions, such as high cholesterol, have both genetic and lifestyle risks that may affect the risk of Alzheimer’s disease.”
There are different types of Alzheimer’s
There are two main types of Alzheimer’s disease, depending on when the symptoms appear.
Late-onset Alzheimer’s affects people age 65 and older, while symptoms of early-onset Alzheimer’s, which is much less common, can begin as early as 30 years of age.
About 74% of late-onset Alzheimer’s cases are due to genetics (lifestyle and environment also affect risk); APOE-e4 is the strongest known risk factor.
Early-onset Alzheimer’s symptoms affect less than 10% of all people with the disease. Genes play an even bigger role here, Mayeux said, but not necessarily APOE-e4. Three genes associated with the early onset of Alzheimer’s are amyloid precursor protein (APP) on chromosome 21, presenilin 1 (PSEN1) on chromosome 14, and presenilin 2 (PSEN2) on chromosome 1.
Although Alzheimer’s is hereditary, a parent with APOE-e4 will not necessarily pass the gene on to their child. Or they could have the gene and pass it on but not get the disease, Mayeux said, it’s very unpredictable.
That is one reason why many experts I do not recommend getting tested for APOE-e4although they sometimes recommend testing for genes involved in the early onset of Alzheimer’s.
APOE-e4 is not the only gene implicated in the disease either. “The most recent research suggests that there are about 50 different locations in the genome that could contain genes that increase Alzheimer’s risk,” Mayeux said.
There are three types of APOE
There are several different versions of the APOE gene, and you inherit two copies, one from each parent.
APOE-e3, the most common, does not appear to affect Alzheimer’s risk one way or another. APOE-e2 can actually diminish the risk of Alzheimer’s, but it is rare.
While APOE-e4 is the strongest genetic risk factor for late-onset Alzheimer’s, having the gene doesn’t mean you’ll definitely develop Alzheimer’s, according to the National Institute on Aging.
If you live to age 65, your chance of getting Alzheimer’s disease at some point in your life is about 15 percent, Scharre said. That is if he doesn’t know your APOE-e4 status. If you do, things change.
If the two alleles you inherit are APOE-e2 or APOE-e3, your risk drops to 9%, Scharre said.
If you have an APOE-e4 allele, your risk rises to 29%; if you have two APOE-e4 alleles, your risk increases to 58%, he said, “but that still means there’s about a 40% chance that you won’t develop Alzheimer’s disease.”
Because Hemsworth has inherited two copies of APOE-e4, one from his mother and one from his father, his risk approaches 58%.
How common are APOE variants?
About 75% of the population has APOE-e3, which does not confer risk. About 25% have one or two copies of APOE-e4. Only 2% to 3% of people have two copies of APOE-e4.
Having one copy increases the lifetime risk of Alzheimer’s by two to three times. Having two raises your risk five to ten times. But he still has to make it to age 60 or older to see the diagnosis come to pass, if it ever does, Mayeux said.
The APOE gene is involved in the transport of cholesterol. According to research published in Science Translational Medicine, the APOE-e4 variant causes lipid (fat) imbalances in the brain that contribute to dementia. APOE-e4 also increases the risk of cardiovascular disease.
Should I get tested?
As we said, many experts do not recommend getting tested, because APOE-e4 is not a cause of Alzheimer’s disease; it’s a risk factor, and there’s a lot of uncertainty that influences who gets it and who doesn’t.
Hemsworth learned of his APOE-e4 status, which was obtained through a genetic test conducted for the Limitless docuseries, but most of us aren’t filming a longevity docuseries. Does genetic testing have a role in the real world?
While the tests are accurate, they do come with a number of caveats, Scharre said. “They are not normally used in the clinic.”
It is very different from testing for BRCA1 or 2, genes that can increase the risk of breast and ovarian cancer. “That genetic evaluation can dictate the therapy, and that’s an important step,” Mayeux said. “At this point, many of us do not encourage genetic testing. If there is any value in genetic testing, it is in helping you decide to participate in a clinical trial or take preventative measures.”
If you decide to get tested, you should consult with a genetic counselor before and after, in accordance with the Alzheimer’s Association. Experts can help contextualize a home test, and running a test without an expert can cause a lot of unnecessary stress.
Treatment and prevention of Alzheimer’s.
One of the reasons people don’t recommend trying the variant is that there are currently no very effective treatments for Alzheimer’s on the market.
At the end of November, investigators published efficacy data on a new monoclonal antibody, lecanemab, that can slow the rate at which the disease progresses. The Food and Drug Administration is reviewing the drug for approval and more progress is expected. An intravenous drug, aducanumab, is already on the market under the brand name Aduhelm.
There are three drugs commonly prescribed for memory symptoms: donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), although they can have side effects.
There are ways to reduce your risk of Alzheimer’s even if you have APOE-e4, Mayeux said. Many of the same behaviors that have been shown to protect the heart also protect the brain, namely exercise and healthy eating, such as the Mediterranean diet.
“There are pretty good studies that support these observations,” Mayeux said.
In addition to exercise, avoiding smoking and excessive alcohol, managing high blood pressure and blood sugar, and preventing and managing hearing loss can also help. reduce the risk of Alzheimer’s disease.
For his part, Hemsworth told Vanity Fair that the genetic test results may actually have been a blessing because he can work to make lifestyle changes that can help fend off disease. ●