Additional file 4: of Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Figure S3. Dot plot graph of semiquantitative assessment of neurodegeneration and DPR. Note that X axis is neurodegeneration score (0 to 3), Y-axis is density of DPR. FCtx - frontal cortex, DF - dentate fascia, CA4 - cornu ammonis sector 4. (TIF 1325 kb

Additional file 7: of Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Figure S5 Comparison of immunostaining with aDMA between C9ORF72 cases and non- neurodegeneration control in parahippocampal cortex. The nuclear signal of aDMA is variable in both cases and controls. Note sparse cytoplasmic inclusions labeled with aDMA in in C9ORF72 cases (arrows). Scale bar represents 50 ΟM. (TIF 2898 kb

Additional file 1: Figure S1. of A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD

Relative quantification (RQ) values of mouse beta-actin, GAPDH and 18S endogenous controls in C9-BAC mouse cortex across different age groups are shown (A). Absolute copy number of human C9ORF72 transcripts per microliter in C9-BAC mice as determined by digital droplet PCR (B), one-way ANOVA (p < 0.001) and Bonferroni’s multiple comparison test was performed between neonatal (0wks) and the remaining age groups, significance is indicated by p < 0.05 * and p < 0.01 **. (JPEG 238 kb

Additional file 2: Figure S2. of A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD

Copy number variation analysis for human C9ORF72 transgene in C9-BAC mouse brain cortex with hypermethylated (me+), unmethylated (me-) promoter and wild-type mouse (WT). (JPEG 142 kb

Additional file 3: of Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Table S1. Quantitative assessment of DPR density by color deconvolution algorithm in clinicopathologic subgroups of C9ORF72-related disease. In frontal cortex, p = 0.019, FTLD vs. FTLD-MND. In CA4, p = 0.055, FTLD vs. FTLD-MND. In CA2/3, p = 0.03, FTLD vs. FTLD-MND. Significant p-values (< 0.05) are indicated in bold. All variables were analyzed with Kruskal-Wallis ANOVA on Ranks and data are displayed as median (25th and 75th range). *Statistically significant p-value (p < 0.05); all p-value for ANOVA on Ranks comparison of all three groups. FCtx = frontal cortex, MCtx = Motor cortex, DF dentate fascia, CA hippocampal subfields. (DOCX 15 kb

Additional file 6: of Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Table S2. Correlation between DPR and aDMA inclusions. P-values are from Pearson’s test of correlation. Significant p-values (< 0.05) are indicated in bold. FCtx frontal cortex, DF dentate fascia, CA - cornu ammonis, MCtx motor cortex. (DOCX 14 kb

Additional file 2: of Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Figure S2. Correlation between manual counts and positive pixel burden from color deconvolution in poly-GR staining. Plot shows the correlation of manual counts of neuronal cytoplasmic inclusions and positive pixel burden from color deconvolution in poly-GR staining. The line shows linear regression CD color deconvolution. Ctx frontal cortex, DF dentate fascia, CA - cornu ammonis, MCtx motor cortex. (TIF 2581 kb

Additional file 5: of Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Figure S4. Western blot analysis of aDMA and sDMA in brains of C9FLTD-MND and sporadic FTLD-MND. The high molecular weight aDMA and sDMA signals are visible in c9FTD/ALS, but not in sporadic FTD/ALS cases. (TIF 2960 kb

Additional file 1: of Loss of Tmem106b is unable to ameliorate frontotemporal dementia-like phenotypes in an AAV mouse model of C9ORF72-repeat induced toxicity

Figures S1 through S10. Figure S1. Transcript expression of Tmem106b in Tmem106b deficiency mice at different ages. Figure S2. Tmem106b reduction does not alter the expression of its family members. Figure S3. Tmem106b immunoreactivity in mice with Tmem106b gene interruption using an additional antibody. Figure S4. The body weight of 2R and 66R injected mouse. Figure S5. Tmem106b reduction alone induces astrogliosis. Figure S6. Heterozygous loss of Tmem106b partially rescues 66R injection-induced neuronal loss. Figure S7. pTdp-43 immunoreactivity in 2R and 66R injected mouse brain. Figure S8. Endogenous C9orf72 protein levels in 2R- and 66R-injected mouse brain. Figure S9. Validation of (GGGGCC)66 repeat overexpression and C9ORF72 knockdown. Figure S10. The effect of (GGGGCC)66 overexpression or C9ORF72 knockdown on TMEM106B protein levels in U251 cells. (DOCX 26231 kb