In a homeostatic environment, the gene expression pattern of microglia is mainly controlled by TGF-β signaling with low APOE expression, whereas in aging and in pathological conditions such as AD, MS, and ALS, the microglia phenotype is characterized by high APOE expression with activation of TREM2 signaling consequent to the phospholipid-APOE complex exposure [107] on apoptotic neurons [91,108]. The gene discussed is APOE; the disease is amyotrophic lateral sclerosis.