Fig. 4: Reduced number of mature oligodendrocytes in the amyloid-carrying hippocampus of AD-like mice exhibit compromised myelin ensheathment. | Nature Aging

Fig. 4: Reduced number of mature oligodendrocytes in the amyloid-carrying hippocampus of AD-like mice exhibit compromised myelin ensheathment.

From: Interleukin-12 signaling drives Alzheimer’s disease pathology through disrupting neuronal and oligodendrocyte homeostasis

Fig. 4

a, Feature plots highlighting markers that characterize known oligodendrocyte maturation states. b, Pseudotemporal ordering of oligodendrocytes revealed differentiation along the known maturation trajectory from OPC via NFOL to MFOL and MOL. c, Cell proportion density along the pseudotime suggests a decrease of more mature oligodendrocytes in the amyloid-carrying APPPS1 mouse hippocampus. d, Reduction of oligodendrocytes reaches statistical significance at the stage of MFOL and MOL and is rescued by the absence of IL-12. n = 3 per genotype, df = 2, F = 2.067 for OPC, F = 1.443 for NFOL, F = 6.184 for MFOL and F = 6.705 for MOL; statistical analysis done by one-way ANOVA with Holm–Bonferroni P value adjustment; boxplots show middle, median; lower hinge, 25% quantile; upper hinge, 75% quantile; upper/lower whisker, largest/smallest observation less/greater than or equal to upper/lower hinge ± 1.5× IQR. e, Representative immunohistochemical MBP staining of corpus callosum from 250-day-old WT, APPPS1 and APPPS1.Il12b−/− mouse brains. f, Analysis of MBP mean gray value, normalized by DAPI mean gray value. One-way ANOVA with Tukey’s multiple comparison test, df = 2, F = 7.185, **P = 0.0051. Each symbol represents one mouse. Bars represent mean ± s.e.m. g, Representative ultrastructural images depicting the hippocampal alveus of 250-day-old WT, APPPS1 and APPPS1.Il12b−/− mice. Scale bar, 2 µm. h, Analysis of g-ratio depicting the proportion of the inner axonal diameter to the total outer myelin, Kruskal–Wallis chi-squared = 126.83, df = 2, P < 2.2 × 10−16. i, Myelin sheath thickness of n = 3 mice per genotype, Kruskal–Wallis chi-squared = 23.244, df = 2, P = 8.966 × 10−6. Electron microscopy images were analyzed by Kruskal–Wallis rank-sum test with Bonferroni correction for multiple testing. Bars represent mean ± s.e.m. j, PLS-DA plot of lipidomics data of 120-day-old WT, APPPS1 and APPPS1.Il12b−/− white matter. k, Heatmap of lipidomics data of 120-day-old WT, APPPS1 and APPPS1.Il12b−/− white matter. l, PLS-DA plot of lipidomics data of 250-day-old WT, APPPS1 and APPPS1.Il12b−/− white matter. m, Heatmap of lipidomics data of 250-day-old WT, APPPS1 and APPPS1.Il12b−/− white matter. df, degrees of freedom; IQR, interquartile range; NS, not significant.

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