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. 2024 Jun 24;19:51. doi: 10.1186/s13024-024-00733-9

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — snRNA-seq reveals microglial activation and oligodendrocyte myelination impairment in TBI are rescued by anti-ac-tauK174 immunotherapy. (A) Subcluster analysis of microglia (resolution 0.15) between conditions: WT, PS19-Sham-PBS, PS19-TBI-PBS, and PS19-TBI-Ab Clone 1. (B) Bar graph of cell ratio per condition within each microglia cluster. ****p < 0.0001, ***p < 0.001, **p < 0.01, and *p < 0.05 by one-way ANOVA with Tukey’s multiple comparisons correction within each subcluster. (C) Ingenuity Pathway Analysis (IPA) upstream regulators of MG1 markers. (D) Percentage and average expression levels of disease-associated microglia (DAM) genes (Tyrobp, B2m), and cytokine gene (C1qa) across 4 conditions; scale, log2 fold-change. (E) Subcluster analysis of oligodendrocytes (resolution 0.2) between conditions. (F) Bar graph of cell ratio per condition within each oligodendrocyte cluster. ****p < 0.0001, ***p < 0.001, **p < 0.01, and *p < 0.05 by one-way ANOVA with Tukey’s multiple comparisons correction within each subcluster. (G) Simple linear regression analysis with standard error showing a positive correlation between OL5 markers and disease-associated oligodendrocyte markers (DAO) (R = 0.4, p = 2.7e-6). (H) Heat map of average expression levels of myelination-related genes (Mpb, Sox10, Tcf7l2), IFN-gamma hallmark genes (Arid5b, Auts2, Bpgm, Usp18), and IFN-responsive oligodendrocyte (IRO) markers (Ifi27l2a, B2m) across 4 conditions; scale, log2 fold-change