How Does Genetic Testing for Alzheimer’s Really Work?

A lot of us have heard of genetic testing and might have some idea of what it is. For those of you who are not quite sure, genetic testing is basically the process of looking at a person’s genome for signs, or ‘genetic markers’ as the science world calls it, of a type of disease. Let’s use an example. Say Susan’s mother was diagnosed with breast cancer (we’ll keep it light, though, she is fine now, for the purposes of our story). Cancer, being a heritable disease, or genetic risk, Susan would like to know her chances of developing breast cancer at some point in the future. Either her blood or her saliva would be sent to a genetic testing lab from which researchers would extract Susan’s DNA(her genetic material). Once they have her DNA, they would screen it for a specific genetic mutation related to breast cancer. If Susan has that marker, her chances of developing breast cancer are said to be much higher than not developing the disease. In other words, Susan has a much higher probability of developing breast cancer but that does not mean that she will for sure.

Now, to stay true to the title of the post, let’s juxtapose that onto Alzheimer’s disease, or simply AD.

Again, a lot of people have heard of AD, some know more about it than others. Simply put, AD is brain disease that slowly and progressively destroys brain cells. And since the majority of those brain cells that are affected are located in the area of the brain that controls memory, language and thinking skills, AD’s most noticeable symptoms are memory loss and difficulty speaking. It may eventually lead to death. You may have also heard that Alzheimer’s disease is a form of senile dementia. Dementia is simply an umbrella term for diseases that affect the way people think and interact with each other. AD is the largest category of senile dementia, accounting for up to 70% of cases.

The elderly are at a much higher risk of developing it than younger people, even though it is said that after the age of 85 all bets are off—we are pretty much all at the same risk.

While we don’t yet really know what causes AD

While we don’t yet really know what causes AD, there are some sure risk factors that may make someone more likely to have it. In addition to lifestyle and age, some of these risk factors are a genetic risk or a genetic mutation. This is where yet another term comes into play, namely ‘predictive genetic testing,’ and this is where our AD story is connected to the example with Susan’s mom above. Predictive genetic testing is basically genetic testing of someone who has a relative (by birth) who is diagnosed with dementia. This type of testing is, of course, only available for inherited AD.

More specifically, mutations in several different AD genes have been found that are connected to an increased risk of getting AD. In particular, there are genes called APOE that stands for Apolipoprotein E. What this basically means is that the APOE gene is responsible for the expression of the Apolipoprotein E, a protein that is involved in metabolism. There are several versions of the APOE gene and what researchers have found is that the version of APOE that is most commonly found in AD individuals is APOE-e4. APOE-04 was discovered in 1993 and it is the first gene variation to be connected with an increased risk of AD. It is still considered to have the greatest impact today. The other two versions are APOE-e2 and APOE-e3.

However, that’s not where the story ends. There are three other genetic variants (and we won’t get into them too much as they are so very rare) that are associated with early-onset AD, meaning individuals younger than 40 or 50 years of age getting the disease. These are APP, PS1, and PS2.

It should be pointed out, however, that if someone has the mutations or variations or genetic markers—whichever term you prefer—they are not going to get AD for sure. It simply means that they are at a higher risk.

So, what does all this mean?

Doctors are not very likely to order a genetic test for a patient who does not show any symptoms of cognitive decline, even if they know that AD runs in their family.

However, if someone really wants to know their genetic profile, a company called 23andMe has started offering genetic tests for people. While at first, this seems appealing—why wouldn’t you want to know what your mental future holds—disclosing someone’s genetic information comes at a risk. Once people receive their DNA results—in other words, once their DNA palms are read, so to speak—they are pretty much on their own unless they decide to receive genetic counseling by someone who can explain to them what all that means. So, while you may think it is exciting to know which disease possibly awaits you in the future, think again if you are the kind of person who would take it in stride or are you someone who will stress out about it. Finding out the future of your health is not always a relief. Some people do find it informative—they adjust their lifestyles and mindsets accordingly. On the other hand, others are not as strong.

For AD, it is especially tricky—not all lifestyle changes are guaranteed to help.

All of this also begs the question of just how relevant genetic testing is for a disease that, once symptomatic, only progresses to become worse. There is currently no medication for it on the market so genetic testing only serves as a confirmation rather than a diagnosis based on which next steps can be taken.

Overall, however, as with many other diseases, AD falls into a category that can certainly be genetically tested. The question is how relevant are the findings in the long run and big picture?

Laura Day