Conversely, one study proposes that suppressing TREM2 activation in neurodegenerative disease may be protective, since TREM2 signaling through the TREM2–Apolipoprotein E (ApoE) axis drives microglia toward the MGnD phenotype and promotes neuronal loss [90,128] (Figure 3A). This evidence concerns the gene TREM2 and neurodegenerative disease.