However, the chronic phase (days 20+) most closely models progressive MS, as microglia exhibit dynamic phenotype switching: TREM2/APOE-mediated lipid clearance and P2Y12R-PI3K/Akt signaling promote repair, while P2X7R-NLRP3 inflammasome activation perpetuates tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)/IL-18 secretion and chronic inflammation (5, 11–13). Here, APOE is linked to myeloid sarcoma.