TREM2 expression level is critical for microglial state, metabolic capacity and efficacy of TREM2 agonism

Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed…

• AF
  Alzheimer Forschung Initiative
• DF
  Deutsche Forschungsgemeinschaft

  Awards: HA1737/16-1, EXC 2145, 457586042, ID 390857198, 390857198, EXC 2145 SyNergy
• LM
  Ludwig-Maximilians-Universität München
• HU
  Hans und Ilse Breuer-Stiftung