Fig. 6. HDAC6 depletion accelerates tau pathology and neurodegeneration.

Representative IHC images of pathological tau detected with the MC1 (a), phosphorylated tau (AT8) (b), and total tau (Tau 12) (c) antibodies in the cortex (top panels) and hippocampus (bottom panels) of 12-month old WT, PS19, and PHK mice. Representative images are shown from n = 3 mice per genotype. Scale bar = 50 μm (a–c, scale bar is identical for both hippocampus and cortex). d ThS-positive tau pathology (green) is double-labeled with total tau (TAUY9, red) and DAPI (blue) to highlight cortical amyloid burden. The high magnification inset depicts a neuron with robust tau pathology. e Quantification of MC1 and AT8 immunoreactivity in the hippocampus and ThS-positive inclusions in the cortex (n = 3 mice per genotype). Error bars represent means ± SEM. Statistical analysis was performed using two-sided unpaired t-test and normalized to PHK. f Quantification of hippocampal area using total hippocampus, dentate gyrus, and CA brain area from 12-month-old mice (n = 4 mice per genotype). Measurements were performed in an unbiased manner using ImageJ software. Statistical tests: one-way ANOVAs were performed with Tukey’s test for multiple comparisons among groups. Data shown represent means ± SEM normalized to WT. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Source data are provided as a Source Data file.