What can genetic testing really tell you about your risk of getting Alzheimer’s disease?
By Lillie Mermoud
As genetic testing has become more accessible and scientists begin to better understand how Alzheimer’s disease develops, genetic testing to learn your risk for Alzheimer’s disease has become increasingly popular.
It’s understandable to be worried about your risk when it’s trending in the news or if you have a loved one suffering from this devastating disease.
Before making a decision about genetic testing for Alzheimer’s disease, it’s important to know what these tests actually look at, what the potential benefits are, and what limitations currently exist.
The genetics of Alzheimer’s disease
Alzheimer’s disease is a complex disorder and does not have a single, clear genetic cause. Instead, Alzheimer’s disease can be triggered by multiple genes, as well as lifestyle and environmental factors.
Everyone has a 10 to 15 percent risk of developing Alzheimer’s disease during their lifetime. Not everyone who is diagnosed with Alzheimer’s disease has a family history of the disease. Individuals with a parent or sibling who was diagnosed generally have a 10 percent higher risk of developing Alzheimer’s than those who don’t, elevating their risk to 20 to 25 percent.
Since many genes and lifestyle habits likely play a role in Alzheimer’s disease, having a genetic risk factor isn’t a guarantee you’ll get it. Likewise, not having an identifiable genetic risk doesn’t mean you’re in the clear.
What genes are linked to Alzheimer’s disease?
Researchers have identified several genes that are linked to Alzheimer’s disease. Risk genes, such as APOE and its variants, could increase your likelihood of getting Alzheimer’s, whereas deterministic genes, such as APP, PSEN1, and PSEN2, are known to cause Alzheimer’s and are strong predictors of your likelihood of developing the disease. Deterministic genes are extremely rare.
If you have a parent, sibling, or grandparent who was diagnosed with Alzheimer’s disease, it’s important to consider the age at which your family members started showing symptoms. Whether your loved ones developed Alzheimer’s disease early in life, between the ages of 30 and 60, or after 65, can be a clue to whether there are genetic contributors to their disease.
Early-onset Alzheimer’s disease
Around 5 percent of people with Alzheimer’s disease have early-onset Alzheimer’s, a form of the disease that develops before the age of 65. An even smaller number, estimated at 1-3% of all cases of Alzheimer’s disease, is due to variants in genes associated with early-onset familial Alzheimer’s disease (EOFAD).
Variants in the APP, PSEN1, and PSEN2 genes are linked to early-onset forms of the disease and are known to elevate your risk of developing Alzheimer’s disease to almost 100 percent.
A person only needs to inherit one copy of a disease-causing variant in one of these genes from their mother or father in order to develop the disease. If a parent has one of these genetic variants, they have a 50 percent chance of passing it to each of their children. Anyone who inherits one of these gene variants is expected to develop Alzheimer’s disease at an early age.
Late-onset Alzheimer’s disease
Most people who develop Alzheimer’s disease have late-onset Alzheimer’s, which generally develops after the age of 65. The most common gene linked to late-onset Alzheimer’s disease risk is APOE.
The APOE gene comes in several forms:
- APOE E1: This form is so rare that it has only been found in a handful of people.
- APOE E2: This form is the least commonly reported and is thought to reduce the risk of developing Alzheimer’s disease
- APOE E3: The most common form, E3, neither increases nor decreases the risk of developing Alzheimer’s disease and is not thought to play a role in disease risk
- APOE E4: While E4 does not cause Alzheimer’s disease, it increases your risk of developing the disease.
Like most genes, you inherit one copy of the APOE gene from each of your parents, which means you have two copies of the gene. It is possible to inherit one copy of the E4 allele, or to inherit two copies, which means both parents passed it on. Having one copy of the E4 allele slightly increases a person’s chance to develop Alzheimer’s disease. However, having two copies of E4 increases a person’s risk of developing Alzheimer’s disease up to 50 percent, but it is not a diagnosis and does not guarantee your likelihood of developing the disease.
Only 2 to 3 percent of people have two copies of the E4 allele, making it extremely rare. You might have heard about one celebrity who recently announced he carries two of these alleles: Chris Hemsworth.
Genetic testing for Alzheimer’s disease
Most clinicians, including our team at the Smith Family Clinic for Genomic Medicine, don’t typically recommend genetic testing for late-onset Alzheimer’s disease because of how complex this form of the disease is and how little gene variants can be used to predict your likelihood of developing the disease.
However, if you have a family history of early-onset Alzheimer’s disease, genetic testing for variants in APP, PSEN1, and PSEN2 may help determine your inherited risk. The results can help you plan for the future and potentially allow you to participate in clinical trials for new treatments or therapies.
Testing for APOE variants is becoming increasingly more affordable, making it more accessible to those who are curious about their risk of developing Alzheimer’s disease. These tests are available through direct-to-consumer companies online or through certain genetic clinics like the Smith Family Clinic.
If you’re interested in an APOE test, keep in mind that the results aren’t predictive of whether or not you will get Alzheimer’s disease. 42% of people with Alzheimer’s disease do not have the APOE E4 allele and many who do never develop the disease.
How the Smith Family Clinic can help you in your journey towards understanding your genetic risk for Alzheimer’s disease
Before stressing about your risk of developing Alzheimer’s disease, it can be helpful to talk with one of our genetic counselors at the Smith Family Clinic. We’ll assess your family history, current health factors, and your personal comfort level with the uncertainties involved in genetic testing for Alzheimer’s disease risk.
We can also help you determine whether genetic testing could be beneficial for you and help you understand your potential results if you decide to go through with testing.
