Fig. 1

Construction of an NHP model with AD-like pathology through stereotactic AAV injection into bilateral hippocampi. A Schematic diagram depicting the construction and evaluation process of the rhesus monkey model with AD-like pathology. The stereotactic injection of AAVs was performed between week 9 and week 10. The monkeys are evaluated for changes in tau expression/phosphorylation, neuronal survival, neuroinflammation, blood vessels, hippocampal volume, CSF biomarkers for AD and cognitive functions before and after viral infection. The NHP model construction and initial evaluation process took approximately 21 weeks. B The T1-weighted MRI scans and coronal atlas of the rhesus monkey brain illustrate the coordinates for stereotaxic injection of AAVs. Six sets of coordinates were determined for each individual animal before viral injection based on 3D reconstruction of the monkey brain from T1-weighted MRI scans. EBZ, ear-bar zero. C Representative images of GFP immunostaining show the AAV-induced broad expression of GFP (exogenous gene) throughout the monkey hippocampus 8 weeks after viral injection. The dashed lines outline the edges of the hippocampi. Scale bar, 1 mm. D,E Quantifications of the average transduction efficiencies of the AAVs in terms of hippocampal area coverage by GFP.⁺ cells in different regions of the hippocampus (D) or at different time points after viral injection (E). “n.s.” means “not (statistically) significant” (P > 0.05). One-way ANOVA with Tukey’s post hoc test (D). Student’s t test (E). N = 4