A Tale of Two Genes: Microglial Apoe and Trem2 Anna A. Pimenova, Edoardo Marcora, Alison M. Goate  Immunity  Volume 47, Issue 3, Pages 398-400 (September 2017) DOI: 10.1016/j.immuni.2017.08.015 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 The Transition between Homeostatic and Damage-Associated Phenotypes of Microglia Is Regulated by APOE and TREM2 The homeostatic signature of microglia is controlled by TGFβ signaling and is characterized by low APOE expression. On the other hand, the damage-associated microglial signature (termed “microglial neurodegenerative phenotype” [MGnD] by Krasemann et al., 2017, or “disease-associated microglia” [DAM] by Keren-Shaul et al., 2017) is characterized by high APOE expression and TREM2 signaling activated by anionic phospholipids in complex with APOE on the surface of apoptotic neurons or in lipoproteins (depicted by the blue pentagon) (Wang et al., 2015; Yeh et al., 2016). When Apoe or Trem2 is knocked out in microglia, the microglia response to brain tissue damage is severely blunted. The DAM signature is conserved across aging and neurodegenerative diseases and is triggered by apoptotic neurons and other cellular debris (e.g., myelin debris) that accumulate in these conditions of brain tissue damage. Gene expression markers for each condition are listed. Immunity 2017 47, 398-400DOI: (10.1016/j.immuni.2017.08.015) Copyright © 2017 Elsevier Inc. Terms and Conditions