Fig. 7
Inhibition of p300/CBP Reduces Tau Spreading a–c p300/CBP double knockout reduces fibril-induced tau spreading in primary neurons. a Representative immunofluorescence staining with MC1 and MAP2 antibody in p300F/F/CBPF/F primary neurons infected with AAV-P301S hTau and lenti-ctrl or lenti-Cre, and treated with synthetic tau fibrils (K18/PL, 100 nM). Negative controls (PBS-treated, AAV non-infected) are included. Scale bar: 100 μm. b Percentage of MC1-positive neurons, normalized to control. ***p < 0.001, unpaired t test. c Number of valid (live) nuclei, normalized to control. n = 9 wells from two independent experiments. d–k Inhibition of p300/CBP reduces tau spreading in PS19 mice. d Schematic diagram of stereotaxic injections in the hippocampus of 3–4 mo PS19 mice carrying p300F/F/CBPF/F. Tau fibrils (K18/PL) were injected into left CA1 (seeding side). AAV-Cre or AAV-GFP were injected into right dentate gyrus (spreading side). e Representative images of immunostaining with acH3K18 antibody in the hippocampus after AAV-GFP (control) and AAV-Cre injections. Scale bar: 200 μm. f Quantification of acH3K18-positive area (normalized to Hoechst) on the spreading side (AAV-injected) normalized to the seeding (fibril-injected) side of hippocampus. g Representative images of immunostaining of MC1 in the hippocampus (CA3) and cortex (entorhinal) after AAV-GFP and AAV-Cre injections. Scale bar: 250 μm. h, j Quantification of MC1-positive area of hippocampus (h) and cortex (j) on the spreading side (AAV-injected) normalized to the seeding (fibril-injected) side. i, k Pearson correlation analysis of acH3K18 signal in the AAV-injected hippocampus with MC1 signal in the hippocampus (i) and cortex (k). n = 7 slices from 9 (AAV-GFP) or 8 (AAV-Cre) mice per group. (f, h, j) ***p < 0.001, unpaired t test. Values are means ± SEM