APOE4 and APOE3 gene variants linked to at least 7 in 10 Alzheimer’s cases, study suggests

You may have heard of the APOE gene, which previous research has linked to Alzheimer’s disease risk. We each have two copies of the gene, and there are different versions – the most common of these are called APOE3, APOE4 and APOE2.

APOE4 is the strongest known genetic risk factor for late-onset Alzheimer’s which typically occurs after the age of 65, while previous research has indicated APOE3 is less likely to affect our risk.

Now, evidence from a new study published in npj Dementia suggests that both APOE variants could play an even greater role in Alzheimer’s risk than previously thought.

What did the study find?

Alzheimer’s Research UK scientist Dr Dylan Williams and his team at University College London analysed health data from over 450,000 people, to find out how many cases of Alzheimer’s and dementia are linked to APOE3 and APOE4 variants.

Their new analysis suggests that APOE4 and APOE3 could account for over 7 in 10 cases of Alzheimer’s. The researchers also estimated that these two gene variants could be linked to nearly half (45%) of all types of dementia.

Dr Sheona Scales, Director of Research at Alzheimer’s Research UK, commenting on the research says: “This study provides important insights into the link between variants of the APOE gene and risk of Alzheimer’s disease and dementia.

“Evidence showing that APOE3 is contributing to Alzheimer’s and dementia risk is especially significant, as this variant has previously been considered to have a ‘neutral’ effect. However, it’s important to note that not everyone with these APOE gene variations will go on to develop dementia, as other risk factors also have an influence.”

So, what do these results mean? We take a closer look at what this study tells us about APOE and dementia risk.

1. Does this mean everyone with either the APOE3 or APOE4 gene will get Alzheimer’s?

The APOE gene is linked to Alzheimer’s risk but having APOE3 or APOE4 does not guarantee you will develop the disease. In fact, most people carry either APOE3 or APOE4 variants, with APOE3 being the most common version. Many people with these variants do not go on to get Alzheimer’s.

Dr Scales explains: “Although this study highlights that more Alzheimer’s cases are linked to the APOE3 and 4 gene variants, not everyone will develop the disease as there’s a complex relationship between genetics and other risk factors for dementia.”

Dr Dylan Williams, lead author on the study, adds: “In addition to the need for more research addressing APOE’s own role in Alzheimer’s, understanding what modifies the risk people inherit from their APOE genes is another crucial question for dementia researchers to grapple with. For example, research shows that nearly half of global dementia cases could be prevented or delayed by addressing certain modifiable risk factors, such as social isolation or managing high cholesterol. With complex diseases like Alzheimer’s and other diseases that cause dementia, there will be more than one way to reduce disease occurrence.”

2. What more can we learn about APOE3 and APOE4 variations?

Alzheimer’s is driven by several different disease processes and we still don’t fully understand how APOE3 and APOE4 affect the biology of the disease.

“A lot of further questions have arisen from this research,” says Dr Scales. “For example, this study focused on data from people of European ancestry, and future studies could provide insights into APOE variants’ effects in other ethnic groups.

“Despite APOE being linked to Alzheimer’s, very few treatments in clinical trials target this gene directly,” Dr Scales continues. “Further research could explore whether targeting these variants could be a promising avenue for treatment and prevention of dementia.”

 

3. Can I get tested to find out if I have APOE3 or APOE4?

“Because of the complexity of Alzheimer’s risk, APOE testing is not available on the NHS for people worried about their risk of developing Alzheimer’s in the future,” Dr Scales points out.

Having one or more copies of APOE3 and APOE4 will not guarantee that someone will develop Alzheimer’s or dementia. Also, it is still possible for people with other variants of APOE to get dementia.

Dr Scales advises: “We cannot change which variants of APOE we have, but there are still steps we can all take to lower our dementia risk as much as possible. It is never too late to start making positive changes to protect our brain health.”

Our dementia information explains more about genes and dementia, and what we know about APOE’s role in Alzheimer’s risk.

 

4. What research is Alzheimer’s Research UK funding to explore APOE further?

We are continuing to support Dr Dylan Williams’ research into looking at how genetics alongside lifestyle and ethnicity affect our dementia risk.

Meanwhile, Dr Suman De at the University of Sheffield is looking at how a rare, protective version of the protein encoded by the APOE gene interacts with amyloid compared to more common variants. Understanding how this protective gene variant may affect the build-up of amyloid could help researchers develop more personalised and effective treatments in the future.

If you are at all concerned about your risk of Alzheimer’s or dementia, you can speak to your GP. Or contact our Dementia Research Infoline on 0300 111 5111 or email infoline@alzheimersresearchuk.org