Trem2 expression in myeloid cells occurs with plaque association. (a) Trem2 expression is observed in myeloid cells (Iba1 positive) associated with plaques (stained with Methoxy-X04) in APP23 (shown) and APPPS1 mice (not depicted). Images are maximum projections of confocal z-stacks (insets show representative high-magnification images of a single confocal plane in plaque-associated cells). (b) Maximum projection of confocal z-stack in 4-mo-old APPPS1/TK− animals shows Iba1-positive cells expressing Trem2 in APPPS1/TK− animals, whereas nonplaque-associated infiltrating monocytes do not express Trem2 in APPPS1/TK+ mice. (c) APP23/TK− as well as APP23/TK+ animals repopulated before Aβ deposition show plaque-associated myeloid cells positive for Trem2 at the age of 10 mo. Bars: (a) 30 µm; (b and c) 20 µm. Immunostaining was performed for n ≥ 4 randomly chosen animals and replicated three times.