APOE and Alzheimer disease: Recently, APOE was found to be a ligand of TREM2 and bind to TREM2 with a high affinity.181 Krasemann et al. found that APOE can bind with the intracellular domain of TREM2 and switch microglia from a homeostatic phenotype to neurodegenerative phenotype in multiple neurodegenerative models including AD, indicating APOE-TREM2 pathway as a proinflammatory signaling.182 Except microglia and astrocytes, APOE was also found to regulate the activation of pericytes.