Fig. 8

Various vascular abnormalities and damages throughout the monkey hippocampus after hTau overexpression. A,B Representative images of laminin immunostaining indicate vascular basement membrane thickening and abnormal vascular morphology alterations in the monkey hippocampus after hTau overexpression. Insets show higher magnification images of the blood vessels in the hippocampus (A). Many vascular abnormalities, such as string vessels (B, open arrows), vessel occlusion (B, open arrowheads), tortuosity, stenosis and bulging of the vascular walls (B, closed arrowheads), emerged after hTau overexpression. Scale bar, 1 mm (A, left), 500 mm (A, inset, right) and 50 mm (B). C,D Representative images of PECAM1 immunostaining suggest vascular degeneration and damage in the monkey hippocampus after hTau overexpression. There were significantly more disintegrated blood vessels in the monkey hippocampus after 6 weeks of hTau overexpression. Insets show higher magnification images of the blood vessels in the hippocampus (C). The progressive vascular degeneration is mainly characterized by blood vessel ruptures (D, arrows) and disintegration (D, arrowheads). Scale bar, 1 mm (C, left), 500 mm (C, inset, right) and 20 mm (D). E Representative images of AQP4 and GFAP staining show relatively diffuse AQP4 expression and substantial astrocytic endfeet retraction from blood vessels in the monkey hippocampus after hTau overexpression. Normally, astrocytic endfeet wrap blood vessels (open arrowheads) with AQP4 water channels on astrocytic endfeet, forming ring-like structures (closed arrowheads). After tau overexpression, AQP4 signals become relatively diffuse (closed arrows), and AQP4.⁺ endfeet detach from the blood vessels (open arrows). Scale bar, 20 mm. F Quantification of the percentage of blood vessels with basement membrane thickening or distinct morphological changes in the monkey hippocampus. ***P < 0.001. One-way ANOVA with Tukey’s post hoc test. N = 6. G Quantification of the percentage of blood vessels with significant structural damage and disintegration in the monkey hippocampus. Note that the percentages of basement membrane thickening, morphologically abnormal, damaged or degenerated blood vessels in the monkey hippocampus after hTau overexpression were significantly higher than the percentages in the control monkey hippocampus. ***P < 0.001. One-way ANOVA with Tukey’s post hoc test. N = 6