APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia. (https://pubmed.ncbi.nlm.nih.gov/38480892/)

These scientists wanted to understand how certain genes related to fat metabolism in the brain might be connected to Alzheimer's disease, which is a condition that affects the brain and memory. They studied brain tissue from people with Alzheimer's disease and found a special type of brain cell called microglia that had a lot of a specific enzyme called ACSL1. They noticed that this enzyme was more common in people with a specific genetic risk factor for Alzheimer's disease.

To learn more, the scientists grew microglia cells in the lab and exposed them to a substance called fibrillar Abeta, which is known to be involved in Alzheimer's disease. They found that when these cells were exposed to fibrillar Abeta, they started making more of the ACSL1 enzyme and storing more fat inside the cells. They also discovered that these fat-filled microglia cells released harmful substances that could damage other brain cells.

Overall, the scientists believe that these findings could help develop new treatments for Alzheimer's disease by targeting the build-up of fats in microglia cells and the harmful substances they release.

Haney MS., Palovics R., Munson CN., Long C., Johansson PK., Yip O., Dong W., Rawat E., West E., Schlachetzki JCM., Tsai A., Guldner IH., Lamichhane BS., Smith A., Schaum N., Calcuttawala K., Shin A., Wang YH., Wang C., Koutsodendris N., Serrano GE., Beach TG., Reiman EM., Glass CK., Abu-Remaileh M., Enejder A., Huang Y., Wyss-Coray T. APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia. Nature. 2024 Apr;628(8006):154-161. doi: 10.1038/s41586-024-07185-7. Epub 2024 Mar 13.