Over the past few months, there have been two big stories in the news concerning Alzheimer’s disease, a devastating brain disorder that destroys memory and the ability to perform simple tasks. The first came from Thor himself, actor Chris Hemsworth, who revealed he has two copies of the APOE4 gene, which has been connected to increased risk for the disease. This led to increased search engine traffic looking for information about APOE genetic testing and how to get tested. But it turns out that it’s not that simple.
Firstly, APOE (apolipoprotein E) is only partially responsible for the risk associated with Alzheimer’s disease (AD), and then, the gene has 3 common variants. We receive one variant from each parent. In Chris Hemsworth’s case, he got a copy of the E4 variant associated with the higher AD risk from both mum and dad. Having two copies of E4 does put Chris at higher risk than, say, someone with E2/E4 or E3/E4. But here’s where it gets a bit more complicated. According to healthcare.com, APOE is not deterministic. So, being E4/E4 does not mean he’s automatically going to develop AD. Nor does not having E4 mean that AD risk is eliminated. In fact, 30-40% of people with clinically diagnosed AD are E3/E3.
So, how helpful is genetic testing for AD?
Well, the first thing to consider is the choice of test as evaluating other genetic markers of the disease, not just the APOE gene, is key. The Alzheimer’s Risk Test, powered by genoSCORE™ (ART), generates what is known as a Polygenic Risk Score because over 100,000 genetic variations are assessed to compute a single genetic risk score for Alzheimer’s disease. Latest results show that ART can identify those at risk of AD, regardless of their APOE status. Not only were the E4/E4 carriers categorized as high risk, but those with other APOE variants were similarly classified, clearly differentiating ART from APOE testing. Polygenic Risk Tests therefore offer more reliable insight into this aspect of an individual’s long-term health.
Lecanemab, a drug to benefit patients with early-stage disease
Going back to the news, the second big story concerned a potential new AD antibody therapy, Lecanemab, jointly developed by Eisai and Biogen. Interestingly, this drug appears to offer greatest benefit to patients with early-stage disease, those with initial symptoms, and it follows that identifying those who are most likely to benefit from treatment will be an important task for doctors. Genetic testing may help with this if, as Professor Sir John Hardy of University College, London, believes “polygenic risk testing is able to be used at the earliest possible time to identify those most likely to benefit from disease-modifying drugs such as Lecanemab”.
Genetic testing for Alzheimer’s disease has clear value, then, when considering the use of an expensive therapeutic. But what about other circumstances? Does it have value for those who are yet to show signs of the disease, like Chris Hemsworth? Potentially, yes, because AD risk isn’t just about genetics. Lifestyle and environmental factors play a significant role, too. Another complication of predicting the onset and progression of the disease. But bear in mind that one of the advantages of genetic testing is that it can provide the motivation to make lifestyle adjustments, or as Prof Hardy says, “knowing your genetic risk can also make clear the importance of lifestyle and environmental risk avoidance”.
First, APOE testing can identify someone’s susceptibility to developing Alzheimer’s disease, but it’s not particularly accurate because only a single gene is evaluated. The Alzheimer’s Risk Test, powered by genoSCORE™ looks at many more genetic markers of the disease and as such, provides a more comprehensive risk score. Second, the benefits of genetic testing include understanding the importance of taking action to reduce the chance of developing the disease, as well as helping identify those most likely to benefit from therapy. Deciding to find out your personal risk score is, well, personal, and being prepared for the result is an essential requirement for anyone who goes down the testing route. Knowledge may be as powerful as Thor’s hammer and using it to make life decisions may be its greatest value.
- Loeppky, J., November 2022. Chris Hemsworth Learned He Has a High Alzheimer’s Risk: What to Know. Healthcare.com https://www.healthline.com/health-news/chris-hemsworth-learned-he-has-a-high-alzheimers-risk-what-to-know