Scientists at University College London have uncovered new evidence suggesting that a single gene, called APOE, may be the key factor behind most Alzheimer’s disease cases.
Their new study, published in the journal npj Dementia, suggests that more than 90% of Alzheimer’s cases might not happen without the influence of this one gene.
The same gene may also play a role in nearly half of all dementia cases. This finding could reshape the way we think about dementia and how to treat or prevent it in the future.
The APOE gene helps make a protein involved in moving fats around in the body and brain. Everyone inherits two copies of this gene—one from each parent.
There are three common versions of the gene, called ε2, ε3, and ε4. These versions combine in different ways to form six possible gene pairs. People with two ε4 genes are known to be at the highest risk of developing Alzheimer’s.
Those with one ε4 and one ε3 gene also have increased risk, while those with two ε2 genes have the lowest risk. For years, researchers mostly focused on the ε4 version as the main problem. But this new study suggests that the more common ε3 version may also play a much larger role than previously thought.
Dr. Dylan Williams, the lead author, explained that the ε3 version has often been seen as “neutral,” but in fact, it still contributes to Alzheimer’s risk—especially when combined with ε4. When the researchers added up the effects of both ε3 and ε4, they found that APOE might be involved in almost every case of Alzheimer’s.
This means that if scientists could figure out how to reduce the risk from ε3 and ε4, they might be able to prevent most Alzheimer’s cases from developing at all.
To reach these conclusions, the researchers looked at data from over 450,000 people across four large studies. This gave them the power to analyze people with rare gene types, such as those who have two ε2 copies.
These people were used as the baseline for comparing Alzheimer’s risk. With this approach, the team estimated that between 72% and 93% of Alzheimer’s cases might not have occurred without ε3 or ε4. About 45% of all dementia cases also appeared to depend on these gene variants.
The researchers admit that their results differed somewhat across the four studies they used. This was due to differences in how Alzheimer’s and dementia were diagnosed, how long the participants were followed, and how they were recruited. Still, when the data were combined, the pattern was clear: APOE appears to be responsible for most Alzheimer’s cases.
This new understanding of APOE could have a big impact on future treatment options. Very few current drugs target this gene, even though it now seems to play such a large role.
Dr. Williams and others believe that more attention should be paid to APOE in drug development. Targeting APOE directly or changing the biological processes it controls could lead to new ways to stop or slow Alzheimer’s before it causes damage.
Even though APOE is important, it is not the only factor that matters. Not everyone with risky versions of the gene develops Alzheimer’s. In fact, even among people with two ε4 copies—the highest-risk group—less than 70% will get the disease in their lifetime. Other genes, lifestyle factors, and environmental risks also play a part.
Things like smoking, high cholesterol, social isolation, and poor diet can increase a person’s chance of developing dementia, regardless of their genes. Many scientists believe that up to half of dementia cases could be prevented or delayed through better lifestyle choices.
Still, this study suggests that APOE’s role in Alzheimer’s has been underestimated. If we can learn more about how it works, and how to protect people who carry the ε3 and ε4 versions, we may be able to prevent millions of dementia cases in the future.
If you care about Alzheimer’s disease, please read studies that bad lifestyle habits can cause Alzheimer’s disease, and strawberries can be good defence against Alzheimer’s.
For more information about brain health, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
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