Dec 2, 2022 - Health + Traits

The APOE Gene and Alzheimer’s Risk

An Australian actor’s recent announcement that he has two copies of the APOE4 variant – which is linked to an increased risk of developing late-onset Alzheimer’s disease – has been making headlines all over the world.

There are actually two types of Alzheimer’s disease: late-onset and early-onset. Late-onset Alzheimer’s is the most common, with symptoms of memory loss, cognitive decline, and personality changes beginning after the age of 65. 

In the United States alone, about 6.5 million people age 65 and older are living with late-onset Alzheimer’s. And that figure is expected to almost double by 2050.

Understanding Alzheimer’s

Late-onset Alzheimer’s is progressive, which means it develops over time. Early stages may result in mild cognitive impairments beyond what would be expected as a natural result of aging.

According to the CDC, symptoms of Alzheimer’s can include:

  • Memory loss that disrupts normal life. 
  • Challenges in planning or solving problems. 
  • Difficulty completing familiar tasks at home, at work, or at leisure.
  • Confusion with time or place. 
  • Trouble understanding visual images and spatial relations.
  • New problems with words in speaking or writing.
  • Misplacing things and losing the ability to retrace steps.
  • Decreased or poor judgment.
  • Withdrawal from work or social activities.
  • Changes in mood and personality.

In later stages, as the disease becomes more severe, these symptoms may become more pronounced, and daily functioning can be severely impaired.

What are the causes?

Late-onset Alzheimer’s disease is influenced by genetics, but genetics is only one component of why some people develop the condition.

Researchers believe that a combination of genetic, environmental, and lifestyle factors all play a role.

The APOE4 connection

The E4 variant in the APOE gene is the most common genetic variant associated with an increased risk of developing late-onset Alzheimer’s disease. Having one copy increases the risk by around threefold. Two copies of the APOE4 gene increase risk by around eight-to 12-fold, although the impact of the E4 variant on risk may vary based on a person’s ethnicity. 

The APOE gene is involved in making a protein called apolipoprotein E, which helps control the levels of cholesterol and fats in the blood. It is not known exactly how the E4 variant increases the risk of late-onset Alzheimer’s disease. 

It’s important to note that having one or two copies of the E4 variant does not mean that you will necessarily develop late-onset Alzheimer’s disease. There are other genetic and non-genetic factors that also play a role, including age, family health history, sex, heart health, and ethnicity.

How can I find out if I have an increased genetic risk?

You can find out whether you may have an increased risk of developing late-onset Alzheimer’s disease based on your genetics with the 23andMe Late-Onset Alzheimer’s Disease Genetic Health Risk report*, which looks for the E4 variant. 

According to our data, APOE is among the most sought-after reports by consumers pursuing their own genetic testing. And research suggests there might be a benefit to knowing your genetic status. A study published in Genetics in Medicine found that while some consumers experienced adverse short-term psychological reactions to receiving APOE results, nearly all experienced long-term benefits from receiving this information and making subsequent lifestyle changes.

How can I reduce my risk of developing Alzheimer’s?

While there is currently no cure for Alzheimer’s, there are six FDA-approved drugs on the market for those who have the condition. Most of these drugs are focused on easing symptoms.  However, research suggests it’s possible to reduce your overall risk of developing the disease by making lifestyle changes.

For example, several 2019 studies found that healthy lifestyle habits like exercise, healthy diet, abstaining from smoking, and cognitive stimulation were associated with a lower risk of developing the disease.

*The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults from saliva for the purpose of reporting and interpreting genetic health risks. It is not intended to diagnose any disease. Your ethnicity may affect the relevance of each report and how your genetic health risk results are interpreted. Each genetic health risk report describes if a person has variants associated with a higher risk of developing a disease, but does not describe a person’s overall risk of developing the disease. The test is not intended to tell you anything about your current state of health, or to be used to make medical decisions, including whether or not you should take a medication, how much of a medication you should take, or determine any treatment.  The Late-Onset Alzheimer’s Disease genetic health risk report is indicated for reporting of the E4 variant in the APOE gene and describes if a person has a variant associated with an increased risk of developing late-onset Alzheimer’s disease. The E4 variant included in this report is found and has been studied in many ethnicities. Detailed risk estimates have been studied the most in people of European descent. 

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