Fig. 3: Deletion of microglial Cx43 alleviates AD pathology and cognitive impairment.

a Mating strategy to achieve Cx43 conditional knockout in microglia (Cx43^mgl-cKO). b Representative Methoxy X04 staining in 9-month-old APP/PS1 and APP/PS1:Cx43^mgl-cKO mouse hippocampus. Scale bar, 50 μm. The number of plaques, percentage of Methoxy X04+ area, the compact plaque percentage, and plaque core area ratio were quantified. N = 5 mice. Statistical test: two-tailed t test. c Representative Aβ (6E10) and dystrophic neurites (RTN3). Scale bar: 10 μm. The number of RTN3+ puncta at different distances from the plaque and the sum number were quantified. N = 32 plaques. Statistical test: two-way ANOVA (intersection curves), and two-tailed t test (sum intersection). d Representative Aβ (Methoxy X04) and dystrophic neurites (LAMP1). Scale bar: 10 μm. LAMP1+ area % at different distances from the plaque and the total area per plaque were quantified. N = 32 plaques. Statistical test: two-way ANOVA (area curves) and two-tailed t test (area per plaque). e Left: Lamp1+ area around compact and fibrillar plaques. N = 33, 27, 46, and 27 plaques. Right: Lamp1 + area around small (0 ~ 300 μm²), medium (300 ~ 1000 μm²) and large (> 1000 μm²) plaques. N = 21, 18, and 21 plaques (APP/PS1), and 27, 29, and 17 plaques (APP/PS1:Cx43^mgl-cKO). Statistical test: two-way ANOVA. f Representative Aβ and Homer1 staining. Scale bar: 10 μm. Homer1+ area percentage at different distances from the plaque was quantified. N = 32 plaques. Statistical test: two-way ANOVA. g MitoSox staining of hippocampal CA1 neuron. Scale bar, 50 μm. MitoSox intensity was quantified and normalized to the WT control. N = 5 mice. Statistical test: two-sided t test. h Novel object recognition test was performed at 9-month-old to examine cognitive function. Statistical test: two-sided t test. i Open field test was performed at 9-month-old to examine the anxiety (Distance in center) and activity traits (total distance). Statistical test: two-sided t test. For behavioral tests, N = 21 (WT), 12 (Cx43^mgl-cKO), 13 (APP/PS1), or 8 (APP/PS1:Cx43^mgl-cKO) mice. 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.