Figure 1.

TREM2 expression is increased around Aβ plaques. (a) A novel Trem2 knockout with a LacZ reporter under the control of the Trem2 promoter was generated. (b–m) TREM2 IHC was performed in WT mice at 2 (b), 4 (c), 6 (d), and 12 mo (e) of age, in APPPS1 mice at 2 (f), 4 (g), 6 (h), and 12 mo (i) of age, and in 5XFAD mice at 2 (j), 4 (k), 6 (l), and 8 mo (m) of age (n = 4–5). Insets show Congo red costaining with arrows indicating plaques. (n–q) TREM2 was also observed around plaques (n, p, and q) but not in regions lacking Aβ deposition (o) in human AD cases (n = 2). Arrows point to Congo red–positive plaques. (r) TREM2 immunoreactivity was not observed in APPPS1;Trem2^−/− mice (n = 7). Insets show Congo red costaining with arrows indicating plaques. (s and t) TREM2 expression was also assessed by qRT-PCR (s; two-way ANOVA, age P = 0.083, genotype P = 0.0036, interaction P = 0.185; Bonferroni-corrected Student’s t tests shown; n = 6–8 per group) and Western blot (t; n = 2–3). Arrowhead indicates position of TREM2-specific band. Error bars indicate SEM. *, P < 0.05. At least three independent experiments were performed for all analyses. Bars, 100 µm (bars in b and n apply to b–p and r).