Notably, the TREM2/APOE pathway (Apoe, Trem2, Fabp5, Gpnmb, and Tyrobp), which is a major regulator driving microglial transition from a homeostatic to a neurodegenerative/neuroinflammatory phenotype in neurodegenerative and autoimmune diseases (Alzheimer’s disease, amyotrophic lateral sclerosis, and MS) (21), was also downregulated in the microglial and macrophage clusters by Ang2 blockade (Figure 3F), which was confirmed by quantitative reverse-transcription PCR (RT-qPCR) (Supplemental Figure 2C). Here, GPNMB is linked to early-onset autosomal dominant Alzheimer disease.