APOE3ch alters microglial response and suppresses Abeta-induced tau seeding and spread. (https://pubmed.ncbi.nlm.nih.gov/38086389/)
These scientists wanted to understand why some people are protected against Alzheimer's Disease, which is a disease that affects the brain and causes memory loss. They studied a person who had a special gene mutation called APOE3ch, which made them resistant to getting Alzheimer's Disease. But they didn't know how this gene mutation worked.
To figure it out, the scientists made special mice that had the same gene mutation as the person they studied. They also made these mice have another feature of Alzheimer's Disease, which is the buildup of a protein called amyloid-beta in the brain. They wanted to see what happens when the mice with the gene mutation have this protein.
They did an experiment where they injected a part of the brain from a person with Alzheimer's Disease into the mice. They found that the mice with the gene mutation had less of the protein and less damage in their brains compared to other mice. They also noticed that the immune cells in the brain, called microglia, were more active and helped to clean up the protein.
The scientists also discovered that the gene mutation made the immune cells better at getting rid of another protein called tau, which is also involved in Alzheimer's Disease. This is important because when tau builds up in the brain, it can cause more damage.
Overall, the scientists found that this gene mutation helps protect against Alzheimer's Disease by making the immune cells in the brain work better and clean up the harmful proteins. This gives us new ideas on how to develop treatments for Alzheimer's Disease in the future.
Chen Y., Song S., Parhizkar S., Lord J., Zhu Y., Strickland MR., Wang C., Park J., Tabor GT., Jiang H., Li K., Davis AA., Yuede CM., Colonna M., Ulrich JD., Holtzman DM. APOE3ch alters microglial response and suppresses Abeta-induced tau seeding and spread. Cell. 2024 Jan 18;187(2):428-445.e20. doi: 10.1016/j.cell.2023.11.029. Epub 2023 Dec 11.