Within an extensive study, researchers found a gene with harmful effects on the brain that could cause Alzheimer’s disease: The apolipoprotein (APOE) gene. It is already known that having one copy of the APOE4 gene increases the risk for Alzheimer’s by two to three times, and having two copies puts people even at a 12-times higher risk.

The role of the APOE gene is usually to provide instructions for creating the protein with the same name. Combined with fats, APOE creates so-called “lipoproteins”, that help to transport cholesterol through our bloodstream.

Now researchers found out that the E4 version of the gene seems to have a damaging effect to the brain and even increases the risk of toxic amyloid beta and tau build-up. To figure out why this version of the gene is more harmful than other variants, scientists needed to locate the differences between E3 and E4 variants, to understand what makes this specific gene so devastating.

For the researchers, there were only two options. The E4 gene either destroys some of the E3 gene functions or it has toxic effects that damages our brain’s functions. To better understand the extent of this problem, they modelled the disease in human cells and examined the effect of APOE4 in human cells for the first time. This is already a huge step for finding out the cause of Alzheimer’s, given that some treatments work perfectly with mice, whereas then, they fail in clinical trials.

« Increased amyloid beta production is not seen in mouse neurons and could potentially explain some of the discrepancies between mice and humans regarding drug efficacy. This will be very important information for future drug development », says Chengzhong Wang.

In the next step, the team started comparing neurons that don’t produce the E3 or E4 variant with cells that had the E4 variant of the protein added. As a result, the first one reacted normally, while the one with the added E4 variant showed Alzheimer’s-like pathologies. This experiment could prove that APOE4 causes the disease.

To continue, researchers had to learn about how to fix the gene, which can cause Alzheimer’s. For this, a “structure corrector” has been developed in order to change the APOE4’s structure more to the APOE3’s gene to prevent Alzheimer’s.

References

• Science Daily. Gladstone Institutes (April 9, 2018). Scientists fix genetic risk factor for Alzheimer’s disease. Available at: https://www.sciencedaily.com/releases/2018/04/180409112559.htm
• Medical News Today. Ana Sandoiu (September 2017). Alzheimer’s: Targeting APOE4 gene may stop the disease. Available at: https://www.medicalnewstoday.com/articles/319492.php