Fig. 7

Decreased clearance and increased accumulation of Aβ throughout the monkey hippocampus after hTau overexpression. A Representative images of Aβ and Iba1 immunostaining suggest the development of Aβ pathology, including intracellular Aβ oligomers and extracellular Aβ plaques, within the monkey hippocampus 10 weeks after viral injection. Higher magnification insets show intracellular accumulation of soluble Aβ (a1) and an extracellular plaque-like structure of Aβ aggregation (a2). Note the Iba1⁺ microglia surrounding the Aβ-accumulating cells and plaques. Scale bar, 200 mm (top) and 20 mm (inset, bottom). B Representative images of Thioflavin-S staining labelling fibrillar Aβ deposits indicate the formation of AD Aβ plaques in the monkey hippocampus 10 weeks after AAV injection. Note the Iba1⁺ microglia and GFAP.⁺ reactive astrocytes gathering around the Aβ plaque. Scale bar, 100 mm. C,D Quantification of Aβ42 (C, green) and Aβ40 (C, red) peptide concentrations, as well as the Aβ42/Aβ40 ratio (D) in monkey CSF determined by Simoa-based biomarker analysis. The Aβ42 level and Aβ42/Aβ40 ratio in CSF were significantly higher in hTau-overexpressing monkeys 12 weeks after AAV injection. *P < 0.05. Student’s t test. N = 5