| Autor: |
Yousef, Ahmed, Robinson, John, Irwin, David, Byrne, Matthew, Kwong, Linda, Lee, Edward, Xu, Yan, Xie, Sharon, Rennert, Lior, EunRan Suh, Vivianna Deerlin, Grossman, Murray, Lee, Virginia, Trojanowski, John |
| Rok vydání: |
2017 |
| DOI: |
10.6084/m9.figshare.c.3873283_d1.v1 |
| Popis: |
Three observed Groups denoted by differences in NeuN and TDP-43 inclusions are seen in IF. Representative images in IF confirms the pattern of staining seen through IHC. In Group 1, NeuN staining remains high with little aggregation of pathology. Pathology increases in Group 2, followed by a simultaneous decrease in both pathology and NeuN in Group 3. Cognitively normal controls maintain a high NeuN level and no pathology. Bar = 100 μL. Figure S2. Immunoblot confirms loss of NeuN protein in Group 3 tissue. After sequential extraction of 2% sarkosyl soluble fraction of mid-frontal and superior temporal cortex grey matter from Groups 1, 2, and 3 tissue, (a) they were immunoblotted with a NeuN antibody. Groups 1 and 2 maintained noticeably higher protein levels than Group 3. (b) The Ponceau S stain of the membrane is shown to demonstrate similar levels of protein transfer. Figure S3. Reactive gliosis increases with increasing Group number. As tissue progresses from Group 1 to Group 3, astrocytosis becomes increasingly evident in the grey matter. Representative images are shown. Bar = 500 μL. Figure S4 Pan TDP-43 is maintained through Groups 1, 2 and 3. Validation of the semi-automated quantification algorithms is shown through (a) representative images of the detection of Pan TDP-43 by IHC (red denotes algorithm recognition in the processed image), (b) log-transformed regressions comparing automatic counts to manual counts (ICC = 0.998), and (c) Bland-Altman plots of the log-transformed data to test mean bias (−0.004) and 95% limit of agreement (−0.070 to 0.062) between automatic and manual counts. FTLD-TDP cerebral cortex is marked by three tissue grouping denoted by differences in the burden of pTDP-43 inclusions and NeuN positive neuronal nuclei stained by IHC. Available (slices sequential to those used for NeuN and pTDP-43 IHC) (n = 94) mid-frontal and superior temporal cortex tissue are selected to investigate staining of Pan TDP-43 in Groups 1-3. Although evidence of neurodegeneration increases from Group 1 to Group 3, we find that (d) Pan TDP-43 is maintained. (e) Quantification of the tissue in each Group also indicates this (Group 1, n = 33; Group 2, n = 14; Group 3, n = 47) (ANOVA, p = 0.1602). Table S1. Focused analyses of bvFTLD-TDP recapitulate spread of pathology and genetic differences. Table S2. Focused analyses of non-bvFTLD-TDP recapitulate spread of pathology and genetic differences. Table S3. Superior temporal cortex tissue recapitulates genetic differences in FTLD-TDP. (PDF 17529 kb) |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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