Fig. 4

Dramatic neurodegeneration and neuronal loss in the monkey hippocampus after hTau overexpression. A Representative images of NeuN immunostaining indicate neurodegeneration and neuronal loss within the monkey hippocampus. The number of NeuN⁺ cells decreased significantly in the monkey hippocampus after 10 weeks of hTau overexpression. The dashed lines separate neighbouring regions of the hippocampus. Scale bar, 1 mm. B Representative images of GFP immunostaining show marked neuritic dystrophy and neuronal damage in the monkey hippocampus after 6 weeks of hTau overexpression. Scale bar, 20 mm. C Quantification of the number of NeuN⁺ cells per mm³ in each hippocampal region of monkeys without hTau overexpression (orange) or with 6 ~ 10 weeks of hTau overexpression (blue). *P < 0.05; **P < 0.01; ****P < 0.0001. “n.s.” means “not (statistically) significant” (P > 0.05). One-way ANOVA with Tukey’s post hoc test. N = 5. D Representative images of Nissl staining suggest neurodegeneration and neuronal loss within the monkey hippocampus. The number of Nissl-stained cells decreased in several regions of the monkey hippocampus after 10 weeks of hTau overexpression. Insets show higher magnification of the DG, CA1, CA3, and CA4 regions. Scale bar, 1 mm (left) and 100 mm (right, inset). E Quantification of the number of Nissl-stained cells per mm³ in each hippocampal region of monkeys without hTau overexpression (orange) or with 6 ~ 10 weeks of hTau overexpression (blue). *P < 0.05; **P < 0.01. “n.s.” means “not (statistically) significant” (P > 0.05). One-way ANOVA with Tukey’s post hoc test. N = 5. F Representative ¹⁸F-FDG PET/MRI fusion images show decreased hippocampal glucose metabolism, suggesting pronounced neuronal degeneration or death 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. G,H Quantifications of hippocampal.¹⁸F-FDG retention (G, original SUV values; H, hippocampus-to-cerebellum SUV ratios) after 6 weeks of hTau overexpression. *P < 0.05; **P < 0.01. Student’s t test. N = 7