TREM2 and early-onset autosomal dominant Alzheimer disease: (Colonna, 2003) Mechanistically, TREM2 is associated with and signals via DAP12, which downregulates the transcription of inflammatory genes like TNFA, IL1B, and NOS2. (Takahashi et al., 2007) TREM2+ macrophages seem to be a highly conserved population, as macrophages with closely similar gene signatures have been described in different tissues and diseases, such as adipose tissue, atherosclerosis and Alzheimer disease.