Fig. 7: TAT-Cx43@LNPs prevent neuropathogenesis at the early stage of AD.

a 3.5-month-old WT and APP/PS1 mice were treated with TAT-Cx43@LNP or with TAT@LNP as control weekly for 8 weeks, before being subjected to histology analysis. b MitoSox Red staining assay was performed on acute brain slices to analyze hippocampal CA1 neuronal oxidative stress. Scale bar, 50 μm. MitoSox intensity was quantified and normalized to the WT control. N = 5 mice. Statistical test: two-sided t test. c Representative images of RTN3 and Aβ staining in the hippocampus. Scale bar, 10 μm. RTN3 + puncta number at different distances from the plaque was quantified. N = 26 (TAT) and 29 (TAT-Cx43) plaques. Statistical test: two-way ANOVA. d Representative images of Aβ and postsynaptic element labeling by Homer1. Scale bar: 10 μm. Homer1 + puncta intensity at different distances from the plaque was quantified. N = 10 (TAT) and 15 (TAT-Cx43) plaques. Statistical test: two-way ANOVA. e Representative images of IBA1 and Methoxy X04 staining. Scale bar, 50 μm. f Quantification of Aβ plaque number. N = 5 mice. Statistical test: two-sided t test. g Higher resolution images of IBA1 and Methoxy X04 staining. Scale bar, 10 μm. h Quantification of the percentage of compact plaque. N = 5 mice. Statistical test: two-sided t test. i For each plaque, the number of periplaque microglia was quantified and normalized to the plaque perimeter. N = 5 mice. Statistical test: two-sided t test. j 3D reconstruction image of the panel g displaying Aβ plaque and the fraction of Aβ plaque within the IBA1 + microglia domain. Scale bar, 10 μm. k The ratio between plaque within microglia and total plaque volume was quantified. N = 5 mice. Statistical test: two-sided t test. Dot plots show mean ± SEM, each data point, and p-value. Significance: *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file.