Studies have long shown that if you carry two copies of the apolipoprotein E (APOE) 4 gene, your chances of developing Alzheimer’s disease are much higher. Now, researchers say in a new study that the gene pair is not just a risk factor, but a genetic form of the disorder.

With two APOE4 genes, you are almost certain to develop Alzheimer’s and will likely start having symptoms at a younger age, according to a new study. published findings in Nature medicine. Given the stronger link between APOE4 and Alzheimer’s, the study authors say different ways may be necessary to help prevent and treat the disease.

What do the findings mean for your Alzheimer’s risk? Should you get tested for the APOE4 gene? Here are answers from neurologists Ayesha Sherzai, MD, and Dean Sherzai, MD, PhD, co-directors of the Alzheimer’s Prevention Program at Loma Linda University in California. The Sherzais also host Your Brain On, a podcast about brain health.

Ayesha Sherzai: It is a genetic configuration mainly responsible for the transport of lipids between cells. There are certain fat molecules that must be transported in and out of the cell. Cells essentially require fats for their infrastructure, for the production of different chemicals, and for their internal functioning. Receptors on cells allow certain fats and proteins to enter and leave them. These are regulated by the APOE4 genotype.

Ayesha Sherzai: Yes, everyone has APOE genes, whether it is APOE2, APOE3, APOE4 or a combination of two types.

Some of the genes work very well. For example, if you have one copy or two copies of APOE2, you don’t tend to have abnormalities in fat metabolism. When you have an APOE3, it is essentially a wash: you are neither protected nor harmed. But APOE4 does a really bad job. If you have one copy of APOE4, you tend to have abnormalities in this lipid transport. If you have two copies of APOE4, it’s even worse.

Dean Sherzai: Genetics influences everything. Things like cholesterol, diabetes, high blood pressure, and terminal diseases like stroke have a significant genetic contribution.. Alzheimer’s is the same. Genetic risk factors determine the results.

In the case of Alzheimer’s, we know that some genes are 100% penetrant genes, meaning that carriers are very likely to develop characteristics of the disorder. [The genes] are: APPLICATION, PSEN1 and PSEN2. If you have those genes, you will have Alzheimer’s before age 65. You can delay it with your lifestyle. [changes], but you will almost certainly get it. In the past, APOE4 was the next highest penetration. We thought it was about 50%, meaning that about 50% of people who live to age 85 and have two copies of APOE4 will get the disease.

This study showed that APOE4 may have greater penetrance than we thought. The findings show that APOE4 genes have the most influence on whether Alzheimer’s develops.

Dean Sherzai: No. It is not 100%. It just highlights the strong association.

The researchers found that by age 65, at least 95% of people with two copies of APOE4 had abnormal levels of amyloid beta in their cerebrospinal fluid, a key early feature of Alzheimer’s disease. Seventy-five percent of people with two copies of APOE4 had brain scans positive for amyloid.

Dean Sherzai: In the general population, approximately 15% to 25% of the population has one APOE4 gene and approximately 2% of the population has two. Between 40% and 50% of people who develop Alzheimer’s, especially late-onset Alzheimer’s, have APOE4 genes related to the disease. (Editor’s note: late-onset Alzheimer’s This is when Alzheimer’s symptoms begin when someone is around age 60 or older).

Ayesha Sherzai: There are tests where you can know your genetic variation. However, these tests are not typically performed in a clinical setting. Your neurologist or primary care physician will not easily order an APOE status. It’s not [generally] covered by insurance.

There are third-party companies you can pay out of pocket to do genetic testing. The decision whether you should go for that or not is entirely up to you. If you have the finances and want to know, you could potentially pay up and do it.

Dean Sherzai: If someone has several family members with Alzheimer’s, there could be an argument for it. Some insurance companies might agree to do so in that context, but it is rare. There is a blood test and a swab test, where they will take some saliva and send it to the lab.

Dean Sherzai: Once Alzheimer’s has fully manifested, it cannot be reversed. What you can do is prevent the disease or slow it down.

Nutrition is a very important part. Study after study has shown that Alzheimer’s disease can be reduced by up to 50% through a predominantly plant-based diet or MIND Diet or a Mediterranean diet.

Exercise can also reduce your risk. But we’re not just talking about walking around the neighborhood. The type of exercise that really tires you out has a significant effect on the brain, particularly strength training. Studies show that people with pre-dementia who strengthened their legs reduced their chances of dementia by more than 40%.

We also know that mental activity is an incredible protector because it connects neurons. We have 87 billion neurons and each of them can make a few connections or between 30 and 50,000 connections. What determines that is exercise and mental activity. Stay engaged, stay challenged, strive for your passions. That’s what maintains connectivity.

Ayesha Sherzai: We always start thinking in our brain when the word “Alzheimer’s” appears. You shouldn’t wait to think about brain health at a certain plateau or at a certain age. Alzheimer’s disease does not start with the first sign of memory problems. It is a condition in which pathological changes occur in the brain 20 to 30 years before the first sign of memory problems. So, those of us in our 30s, 40s, and 50s need to make sure we address our risk factors now so we can have healthy brains later in life.

Talk to your doctor about your cholesterol levels. Understand your blood pressure levels and your hemoglobin a1c. Understand what your numbers are so you can adjust them with lifestyle changes and potentially healthcare treatments, such as medications, if necessary.

Dean Sherzai: It’s about developing resilience. Your brain is a huge building with pillars. After the age of 20, we either tear down pillars or build more pillars that strengthen that brain. For a large majority of the population, and even for those who are at genetic risk, the sooner you start building pillars, the more likely you are to reverse Alzheimer’s or prevent it altogether.

Listen to the Sherzais talk about Alzheimer’s on the WebMD podcast.