Additional file 3: of TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy

MAPK signaling changes detected in 3- month hTau;Trem2 −/− hippocampi despite no differences in tau pathology. Western blot analysis and quantification of hippocampal protein extracts from 3-month hTau (Trem2 +/+ ) and hTau;Trem2 −/− mice (n = 4–6 per group) reveals significant upregulation of ERK1/2 and significant differences in the ratio of pERK1/2/total ERK1/2, and pJNK/total JNK. A reduction in GSK3β was observed in TREM2 deficient mice which lead to significant increases in the ratio of pGSK3β/total GSK3β, although no significant differences were observed between hTau and hTau;Trem2 −/− mice with regard to the total levels of activated GSK3β. Cortices (E,F) from 3-month hTau (Trem2 +/+ ) and hTau;Trem2 −/− mice (n = 4–6 per group) were analyzed using western blot. Quantification of these data revealed no significant differences between genotypes at 3-months in the cortex. At least two independent experiments were performed for each analysis, n = 4–6 mice per genotype; equal males and females. Error bars represent SEM. *, P < 0.05, **, P < 0.01, ***, P < 0.001. (PDF 9791 kb)