APOE2 act as inhibitors to microglial LDAM transition by restricting LD accumulation

Recent studies have suggested the relationship between genetic risk factors related to lipid droplets accumulation such as APOE4 and Alzheimers disease pathology. However, whether certain APOE variants act as inhibitors of transition to LDAM by limiting LD accumulation remains unknown. This paper raises a research proposal for this question by trying to illustrate it in two steps. First, experiments performing immunostaining on mice suggest that APOE2 could limit lipid accumulation, proving that APOE2 could efficiently clear myelin debris and microgliosis is dramatically increased upon acute demyelination. Then, several experiments are performed to prove that limited lipid accumulation could reduce microglial LDAM transition, illustrating that the differences in ability of phagocytosis, ROS production and immune signaling exist if there are differences in the content of lipid accumulation. Finally, some insights about the related therapies are mentioned. If the hypothesis in the proposal is proved to be true, some related potential therapeutic strategies for treating Alzheimers disease would appear.