Tubastatin treatment decreases total human tau levels in the mouse brains with no changes in hippocampal atrophy. Representative images of brain tissue from (A, B, C) saline-treated and (D, E, F) tubastatin-treated rTg4510 mice stained for total human tau levels (H150): (A), (D) cortex, and (B), (C), (E), (F) hippocampus (HPC) at two different magnifications (original magnifications 5×, 10× and 65×). (B, E) Arrowhead, neuropil staining. Scale bar: 200 μm, 50 μm and 20 μm. (G, H, I) Quantification of immunostaining confirmed reduction of tau levels following treatment: (G) cortex (P = 0.055), (H) HPC (*P < 0.05), and (I) entire hemisphere (**P < 0.001); Student’s t test, n = 6. Nontransgenic (ntg) mice showed no immunoreactivity against human tau and were thus excluded from the statistical analyses. (J) Average number of errors made in the radial arm water maze was plotted against the tau load (H150) measured as the percent positive area in tissue, n = 5/6, P = 0.0130, r = 0.690. (K) HPC volume was measured by stereology. The reduced hippocampal volume observed in rTg4510 mice was not affected by the tubastatin treatment (two-way ANOVA, **P < 0.001). Data presented as average +/- SEM.