Tau reduction is equally protective against neuronal loss with amyloid-β deposition. (A) At the time of sacrifice, wet weight of each full brain was analysed immediately after perfusion. APP × rTg4510 DOX brains weighed significantly more than naïve APP × rTg4510 mice with rTg4510 DOX mice show a trend towards an increase in brain weight from the rTg4510 naïve treated mice. Treatment effect F(1,46) = 5.112, P = 0.0285. (B–D) For each mouse, the cortex [B; treatment effect F(1,46) = 12.03, P = 0.0012] and hippocampus [C; treatment effect F(1,46) = 15.41, P = 0.0003) of six sequential sections spaced 400 µm apart were outlined for area and volume calculated. APP × rTg4510 mice treated with DOX showed a significant increase in cortical and hippocampal volume when compared to naïve APP × rTg4510, with rTg4510 DOX mice showing a trend towards increased volume when compared to naïve rTg4510 mice. No significant difference was detected between rTg4510 DOX and APP × rTg4510 DOX treated groups. Cortex (red dashed line) and hippocampus (back dashed line) are highlighted in representative photos (D). (E and F) To assess neuronal counts, the number of NeuN-positive nuclei (nuclei labelled with blue DAPI) in the CA1 portion of the hippocampus was counted in two sequential sections spaced 800 µm apart. Similar to the hippocampal volume analysis, significant, and equal, protection is conferred in rTg4510 and APP × rTg4510 DOX mice [E; treatment effect F(1,46) = 27.21, P < 0.0001]. Representative images showing NeuN (red) and DAPI (blue) in the CA1 region of the hippocampus. Two-way ANOVA, Sidak post hoc analysis. ***P < 0.001, ****P < 0.0001. Each data point represents one mouse. Mean ± SEM.