FISH identifies alterations in gene expression within plaque microenvironment as a result of Trem2 deficiency. a Representative images of FISH analyses of microglia gene expression near amyloid plaques at 6.5 months of age (Tmem119 – red, Csf1r – Pink, Clec7a – Green, Nuclei – Blue, Amyloid plaque - White). The area occupied by the puncta was quantified adjacent to plaques (< 50 μm) as well as away from plaques (> 50 μm) for APP/E3, APP/E3/Trem2ko, APP/E4, and APP/E4/Trem2ko mice. Bar plots showing the area of puncta coverage adjacent to and away from plaques, and line patterning depicting the Z-score of RNA-seq data and FISH data together for Clec7a DAM marker (b & e), Csf1r homeostatic microglia marker (c & f), and Tmem119 homeostatic microglia marker (d & g). FISH analysis by one-way ANOVA followed by Tukey’s multiple comparison test. n = 4 mice per group (equal males and females), an average of 86 plaques analyzed per genotype, bars represent mean ± SEM, and *** p < 0.001; * p < 0.05 using Tukey’s multiple comparison testing.