What is the APOE4 Gene?

The APOE4 gene variant is one of the strongest genetic risk factors for late-onset Alzheimer’s disease. People who inherit one or two copies of APOE4 have a much higher chance of developing Alzheimer’s as they age, compared to those with other variants like APOE3. Researchers estimate that about 164 million people worldwide carry two copies of APOE4, putting them at significantly elevated risk.

APOE4 and Alzheimer’s: A Strong Link

The discovery of APOE4's role in Alzheimer's came in the early 1990s, and it quickly became a focus for scientists. Those with two copies of APOE4 have an 8 to 25 times higher risk of developing late-onset Alzheimer’s. Interestingly, APOE4 doesn't just increase the risk—it also speeds up the accumulation of beta amyloid plaques, a hallmark of Alzheimer’s disease, making it harder for the brain to remove these damaging proteins.

Breakthrough Research on APOE4

New studies are revealing more about how APOE4 contributes to Alzheimer’s. In 2024, a groundbreaking study suggested that APOE4 may be a direct cause of amyloid buildup, not just a risk factor. This finding has pushed scientists to look for treatments targeting the effects of APOE4. Researchers are exploring therapies, including gene-modifying treatments and drugs that can help manage APOE4’s damaging effects on the brain.

The Future of Alzheimer’s Treatments

While current Alzheimer’s treatments, like the recently approved lecanemab, have shown modest benefits, they may be especially helpful for APOE4 carriers. Ongoing research aims to develop more effective ways to treat or prevent Alzheimer’s by targeting APOE4’s impact. This could include RNA-based therapies or even gene-editing techniques to modify the way APOE4 functions in the brain.

These new insights into APOE4 are offering hope to millions of people at risk of Alzheimer’s and advancing the fight against this devastating disease.

Read in full in Science