Fig. 7. Marked reductions in GAT1 mRNA expressing cells in AD cases with dementia.

a Images showing colorimetric in situ hybridization for vGluT1 and GAT1 mRNAs in a control no dementia-CERAD 0 case and a dementia-CERAD 3 AD case. Insets show labeled cells at higher magnification. Calibration bar, 750 μm; 375 μm for inset. b Images showing examples of GAT1 mRNA positive (+) cells that were identified and counted in the analyses; identified cells are overlaid with a small cyan dot. Calibration bar, 100 μm c,d Quantification of vGluT1 and GAT1 mRNA expressing cells in parietal cortex per 10,000 μm² (plots show median values, 25th, and 75th percentiles, and minimum and maximum range). Data shown are based on a 10 µm² size threshold: separate analyses using 30 µm² size threshold yielded similar differences in E/I ratios between groups (Supplementary Fig. S5). GAT1 expressing cells were reduced in the AD dementia-CERAD 3 group (n = 8 AD subjects) versus the control, no dementia-CERAD 0 group (n = 7 healthy controls). P values are from the two-sided Wilcoxon Test. e vGluT1/GAT1 ratios for the same subjects; individual vGluT1 to GAT1 comparisons are presented in Supplementary Fig. S5. The cellular E/I ratio was significantly elevated in the AD group versus controls (**P < 0.01 two-sided Wilcoxon test; n = 7 controls, 8 AD). f Linear correlation between the cellular (vGluT1/GAT1) and transcriptional (DGL4/GPHN) expression E/I ratios for cases with both data sets (see Supplementary Data 6); AD (n = 8) cases, cyan; control cases (n = 7), black.