Fig. 2

(A) Quantification of brain weight at various time points in animals overexpressing wild-type tau (“AAV-Tau”) compared to non-coding control vector (“AAV-STOP”). 3wk AAV-STOP, N = 9; 3wk AAV-Tau, N = 10; 6wk AAV-STOP, N = 10; 6wk AAV-Tau, N = 17; 12wk AAV-STOP, N = 24; 12wk AAV-Tau, N = 21. Unpaired t-tests were used for the 3- and 6-week timepoints, and Mann-Whitney test was used for 12-weeks, depending on results for normality testing. (B) 3D volumetric renderings of lateral ventricles (top) and hippocampi (bottom) from AAV-Tau and AAV-STOP animals at 3 months of age based on MRI images. Quantification of these volumes is shown. 12wk AAV-STOP, N = 5; 12wk AAV-Tau, N = 6. (C) Representative confocal images of NeuN⁺ neurons in three brain subregions, at three time points after neonatal infection. Scale bar, 50 μm. Quantification of relative neuronal density in AAV-Tau compared to AAV-STOP animals by region and age. In all regions: 3wk AAV-STOP, N = 5; 3wk AAV-Tau, N = 5; 6wk AAV-STOP, N = 6; 6wk AAV-Tau, N = 6; 12wk AAV-STOP, N = 12; 12wk AAV-Tau, N = 12. (D) Representative confocal images of DNA damage in hippocampal neurons (CA3) marked by nuclear γH2AX⁺ foci. Quantification of γH2AX⁺ neurons in brain subregions at 6 weeks of age. 6wk AAV-STOP, N = 6; 6wk AAV-Tau, N = 6.

E) Representative confocal images of DLK stress pathway in hippocampal neurons (CA3) marked by nuclear p-cJun signal. Quantification of p-cJun⁺ neurons in brain subregions at 6 weeks of age. 6wk AAV-STOP, N = 6; 6wk AAV-Tau, N = 6.