Fig. 6

Lower amyloid burden in areas with higher CSF influx. a Brain template for analysis of the regional differences. The dorsal, lateral, and ventral regions are marked with different colors. b Representative brain images with amyloid plaque (blue, MX04), 3 k-FITC (green), and 40 k-TMR (red) signals in mid and old Tg mice. Scale bar = 100 µm. c Regional differences in plaque burden. Note that the amyloid burden increases from the ventral (V) toward the lateral (L) and dorsal cortices (D) in both mid and old Tg (mid, p < 0.001; old, p < 0.001, one-way ANOVA). d, e Regional differences in the parenchymal signals of 3 k-FITC (d) and 40 k-TMR (e). Note that the tracer signal is the highest in the ventral region and decreases toward the lateral (L) and dorsal (D) cortices. [3 k-FITC; mid, p < 0.001; old, p < 0.001] [40 k-TMR; mid, p < 0.001; old, p < 0.001]. f, g. Linear regression between amyloid burden and influx signals of 3 k-FITC (f) and 40 k-TMR (g) in mid and old Tg mice. Note the negative linear correlation between the amyloid plaque burden and influx, which is consistent irrespective of the tracer weight and Alzheimer’s disease progression. [3 k-FITC (mid, p < 0.0001, R² = 0.2701; old, p < 0.0001, R² = 0.09102)]; [40 k-TMR (mid, p < 0.0001, R² = 0.2176; old, p < 0.0001, R² = 0.1590)] (n = 9, mid Tg, n = 8, old-Tg, 7 slices/mouse). All data are presented as the mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 One-way ANOVA with Tukey’s post hoc test