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. 2023 Oct 29;26(11):108362. doi: 10.1016/j.isci.2023.108362

Figure 6.

Figure 6

Heterozygous deletion of Tmem106b does not rescue histopathology in 13 months old Grn −/− mice

(A) Representative images of CD68, LAMP1, and CatD from forebrain (FB) coronal sections.

(B) Overall effects of genotype observed for CD68 staining in whole section analysis (FB) p < 0.0001, (HB) p < 0.0001 sections by one-way ANOVA. Grn −/− mice had significantly increased levels of CD68 compared to Wt mice. Tmem +/−, Grn −/− mice did not differ from Grn −/− mice, showing significantly increased levels of CD68 in FB and HB compared to Wt mice. Also, Tmem −/− mice displayed significant increase in CD68 in HB compared to Wt mice.

(C) Lamp1 staining is significantly altered between genotypes in FB p < 0.0001 and HB p < 0.0001 by one-way ANOVA. Grn −/− mice show significantly increased levels of Lamp1 in FB and HB when compared to all other genotypes. Lamp1 levels were partially reduced in Tmem +/−, Grn −/− compared to Grn −/− mice. Tmem −/− mice displayed a significant increase in Lamp1 in HB only.

(D) One-way ANOVA reveals an overall genotype effect on cathepsin D in FB p = 0.002 and HB p < 0.0001. Grn −/− and Tmem +/−, Grn −/− mice have significantly increased levels of cathepsin D in FB and HB when compared to Wt and did not differ from each other.

(E) One-way ANOVA reveals an overall genotype effect of AmCuAg staining HB p < 0.0001 but not in FB. Tmem −/− and Grn −/−mice each had significantly increased levels of AmCuAg in HB when compared to Wt. Tmem +/−, Grn −/− mice did not differ significantly from Grn−/− mice. For histology, n = 5–10 animals/genotype and 4–5 sections/animal/tissue area/stain.

(F) An overall effect of genotype was detected in plasma NFL levels by one-way ANOVA p < 0.0001. NFL was significantly increased in Tmem −/− and Grn −/− mice compared to Wt mice. Tmem +/−, Grn −/− NFL levels did not differ from Grn −/− mice. Tmem +/−, Grn +/− NFL levels were similar to Wt mice. N = 8–14 animals/genotype. Student’s test or Tukey post-hoc ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. All error bars represent S.E.M. Figure created with BioRender.com.