Last month, Chris Hemsworth introduced he was taking a break from appearing after studying he has a gene variant that will increase his threat of growing Alzheimer’s illness. The revelation, which got here by a genetic take a look at carried out for the docuseries Limitless, was not fully stunning, Hemsworth informed Vanity Fair: His grandfather has Alzheimer’s, and the situation is very heritable.
The news got here as a shock, for certain. But it doesn’t imply Hemsworth’s future is foretold, in response to specialists. In reality, his expertise is one motive specialists say you might need to keep away from getting examined for this explicit variant, although the take a look at is an possibility with some mail-in genetic exams.
For one factor, the exams can solely establish threat, not predict who will really develop Alzheimer’s. Conversely, many individuals who develop the illness don’t have this genetic variant, or allele.
The gene, often called APOE-e4, is taken into account a threat issue however not a reason for the illness.
“We know that people who have APOE-e4 [can] live a long life without developing Alzheimer’s,” stated Dr. Richard Mayeux, chair of the neurology division on the Columbia University Vagelos College of Physicians and Surgeons.
Although life-style adjustments like train may help, there are few efficient methods to gradual or delay Alzheimer’s.
“I don’t encourage genetic testing for Alzheimer’s, because if I find that you have a mutation there’s nothing I can do to keep you from getting this disease,” Mayeux said, although “that may change.”
What causes Alzheimer’s disease?
Alzheimer’s is the most common form of dementia, affecting some 6.5 million Americans, most of them 65 and over. That number is likely to double by 2050, according to the Alzheimer’s Association. Experts are still teasing out the causes, but it’s clear that both genes and environmental factors play a role.
“It is a polygenic disorder meaning that there are many genes that may impact getting Alzheimer’s disease,” said Dr. Douglas Scharre, director of the Division of Cognitive Neurology for the Ohio State University Wexner Medical Center. “Lifestyle factors may be separate influencers of getting Alzheimer’s disease. Some conditions, like elevated cholesterol, have both genetic- and lifestyle-related risks that can impact the risk of getting Alzheimer’s disease.”
There are different types of Alzheimer’s
There are two main types of Alzheimer’s disease, depending on when symptoms appear.
Late-onset Alzheimer’s affects people 65 or over, while symptoms of early-onset Alzheimer’s, which is much less common, can start as early as when someone is in their 30s.
About 74% of late-onset Alzheimer’s is 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 linked to early-onset 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 does run in families, a parent with APOE-e4 won’t necessarily pass on the gene to a child. Or they could have the gene and pass it on but not get the disease themselves, Mayeux said — it’s very unpredictable.
That’s one reason many experts do not recommend getting tested for APOE-e4, although they sometimes recommend testing for the genes involved in early-onset Alzheimer’s.
APOE-e4 is also not the only gene implicated in the disease. “The latest research suggests there are close to 50 different locations in the genome that might contain genes that increase your risk of Alzheimer’s,” Mayeux said.
There are three types of APOE
There are several different versions of the APOE gene, and you inherit two copies of it — one from each parent.
APOE-e3, the most common, doesn’t seem to affect Alzheimer’s risk one way or another. APOE-e2 may actually decrease the risk of Alzheimer’s, but it’s rare.
While APOE-e4 is the strongest genetic risk factor for late-onset Alzheimer’s, having the gene doesn’t mean you definitely will 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 lifetime is about 15%, Scharre said. That’s if you don’t know your APOE-e4 status. If you do, things change.
If both of the alleles you inherit are APOE-e2 or APOE-e3, your risk goes down to 9%, Scharre said.
If you have one APOE-e4 allele, your risk goes to 29%; if you have two APOE-e4 allele, your risk goes to 58%, he said, “but that still means that there is about a 40% chance you will not get Alzheimer’s.”
Because Hemsworth has inherited two copies of APOE-e4, one from his mother and one from his father, his risk is closer to 58%.
How common are the APOE variants?
About 75% of the population has APOE-e3, which confers no 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 raises your lifetime risk of Alzheimer’s two- to threefold. Having two elevates your risk five to tenfold. But you still have to make it to your 60s or beyond to see that diagnosis happen, if it ever does, Mayeux said.
The APOE gene is involved in cholesterol transportation. According to research published in Science Translational Medicine, the APOE-e4 variant causes imbalances in lipids (fats) in the brain that contribute to dementia. APOE-e4 also raises your risk of cardiovascular disease.
Should I get tested?
As we said, many experts don’t recommend getting tested, because APOE-e4 isn’t a cause of Alzheimer’s; it’s a risk factor, and there is a lot of uncertainty that influences who does and doesn’t get the condition.
Hemsworth learned his APOE-e4 status, which came through a genetic test done for the docuseries Limitless, but most of us aren’t filming a docuseries about longevity. Does genetic testing have a role in the real world?
While the tests are accurate, they come with a number of caveats, Scharre said. “They’re not typically used in the clinic.”
It’s very different from testing for BRCA1 or 2 — genes that can raise your risk of breast and ovarian cancer. “That genetic assessment can dictate therapy, and that’s an important step,” Mayeux said. “At this point, a lot of us don’t encourage genetic testing. If there’s any value in genetic testing, it’s helping you decide to get into a clinical trial or to take preventive measures.”
If you do decide to get tested, you should confer with a genetic counselor before and after, according to the Alzheimer’s Association. Experts can help contextualize a home test, and taking a test without an expert can cause a lot of unnecessary stress.
Alzheimer’s treatment and prevention
One of the reasons people don’t recommend testing for the variant is that there are no hugely effective treatments for Alzheimer’s currently on the market.
In late November, researchers released efficacy data on a new monoclonal antibody, lecanemab, which may slow down how quickly the disease progresses. The Food and Drug Administration is reviewing the drug for approval, and more advances are expected. One IV 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 lower your risk of Alzheimer’s even if you have APOE-e4, Mayeux said. Many of the same behaviors that have been shown to protect your heart also protect your brain — namely exercise and healthy eating, like the Mediterranean diet.
“There’s pretty good studies that support these observations,” Mayeux said.
In addition to exercise, avoiding smoking and excess alcohol, controlling high blood pressure and blood sugar, and preventing and managing hearing loss can also help cut back your threat of Alzheimer’s illness.
For his half, Hemsworth informed Vanity Fair that the outcomes of the genetic take a look at may very well have been a blessing as a result of he can work on making adjustments in his life-style which will assist fend off the illness. ●