TREM2 expression is differentially associated with microglia and hematogenous monocyte/macrophages proximally and distally located to amyloid plaques

Amyloid-β (Aβ) plaque deposition is a feature of Alzheimer’s disease. Triggering receptor expressed on myeloid cells 2 (TREM2) regulates inflammatory responses by increasing phagocytic activity, and its expression is modulated by inflammation in the brain. One of the ligands for TREM2 is Aβ. TREM2 is highly expressed on myeloid cells, including microglia and peripheral tissue-resident macrophages. Both microglia and hematogenous macrophages interact directly with Aβ plaques. Using our 5XFAD lys -EGFP- ki transgenic mice, we studied the expression of TREM2 in plaques engaging microglia and infiltrating macrophages. We characterized the expression of TREM2 by measuring the protein level of TREM2 in the cortex at three different time points: 1.5, 3, 5, and 7 months of age. We observed a decrease in TREM2 levels in the cortex with disease progression. TREM2 levels were also lower in cells interacting with Aβ plaques compared to cells far from Aβ plaques. Finally, we performed an ultrastructural analysis of microglia and hematogenous macrophages interacting with plaques, which revealed more dystrophic mitochondria and phagocytosed material in hematogenous macrophages than in microglia.