Fig. 2
High levels of tau expression throughout the monkey hippocampus after AAV injection. A Schematic diagram of our engineered AAV constructs (Syn::FLPo and CAG::FRT-hTau) used to express FLPo recombinase, which in turn will activate the expression of hTau. B Representative images of tau immunostaining demonstrate the AAV-induced overexpression of tau in neurons within the monkey hippocampus 6 weeks after viral injection. Compared to that of endogenous tau (left), the expression level of tau in the hTau-overexpressing monkey brains (right) was significantly higher, especially in neuronal somas and apical dendrites. Insets show higher magnification of the CA3 (a1, b1) and CA1 (a2, b2) regions. Scale bar, 1 mm (top) and 20 mm (inset, bottom). C Quantification of the normalized fluorescence intensity of tau staining in the monkey brains. The expression levels of tau in the monkey hippocampus after 6 weeks of hTau overexpression were significantly higher than those of endogenous tau in the control monkey hippocampus. ***P < 0.001. Student’s t test. N = 5. D Quantification of the normalized total tau (green), phospho-tau 181 (red), and phospho-tau 231 (blue) concentrations in monkey CSF determined by Simoa-based biomarker analysis. The CSF levels of total tau, phospho-tau 181, and phospho-tau 231 were significantly higher in the hTau-overexpressing monkeys 12 weeks after AAV injection. *P < 0.05, **P < 0.01. Student’s t test. N = 5. E Representative 18F-T807 PET/MRI fusion images indicate higher tau expression in the monkey hippocampus 6 weeks after AAV injection. The linear colour scale with the standardized uptake value (SUV) range is shown in the right part of the figure. The dashed lines outline the edges of the hippocampi. Scale bar, 1 cm. F,G Quantifications of hippocampal.18F-T807 retention (F, original SUV values; G, hippocampus-to-cerebellum SUV ratios) after 6 weeks of hTau overexpression. *P < 0.05; **P < 0.01. Student’s t test. N = 7