Fig. 5

Substantial and progressive hippocampal atrophy after hTau overexpression. A Representative coronal T1-weighted MRI images demonstrate hippocampal atrophy in monkey brains after 12 weeks of hTau overexpression. The hippocampal area measured in the coronal section shrinks significantly in the monkey brain 12 weeks after viral injection (right). The dashed boxes highlight the hippocampal areas. Scale bar, 1 cm. B Three-dimensional surface reconstructions and the volumes of the right hippocampus of a monkey at 3 different time points throughout hTau overexpression (red, before AAV injection; green, 6 weeks after injection; blue, 12 weeks after injection). This longitudinal study clearly reveals the progressive hippocampal volume decrease after hTau overexpression. The 3D reconstructions and tissue volumes were obtained using Brainsight software (Rogue Research). 3D scale bar, 1 cm in each direction; the rostral-caudal axis is perpendicular to the screen with the rostral direction pointing out of the screen. C Quantifications of the longitudinal changes in the normalized hippocampal volumes defined by MRI scans. Each colour represents one animal. **P < 0.01; ***P < 0.001; ****P < 0.0001. Repeated measures ANOVA with Tukey’s post hoc test. N = 5. D Representative images of coronal vibratome sections (DAPI labelling) showing hippocampal atrophy in monkey brains after 6 and 50 weeks of hTau overexpression. The hippocampal area measured in the coronal section shrinks significantly in the monkey brain 6 (middle) and 50 (right) weeks after viral injection. The dashed boxes highlight the hippocampal areas. Scale bar, 1 cm. E Quantifications of the longitudinal changes in the normalized hippocampal areas measured in coronal vibratome sections. *P < 0.05; **P < 0.01; ***P < 0.001. One-way ANOVA with Tukey’s post hoc test. N = 5. F Quantification of neurofilament light chain (NfL) concentrations in monkey CSF measured by Simoa-based biomarker analysis. The normalized NfL level in CSF was ~ 3.5 times higher in hTau-overexpressing monkeys 12 weeks after AAV injection. ****P < 0.0001. Student’s t test. N = 5