Fig. 6
Loss of perivascular AQP4 localization impairs CSF-ISF exchange and promotes amyloid β deposition. A Representative images of the 10 kD (top) and 70 kD (bottom) CSF tracer distribution in the wild type and Snta1−/− mice 90 min after intracisternal injection of 10 kD (Cascade Blue) or 70 kD (Texas Red) dextrans. B CSF tracer area coverage was generally reduced in Snta1−/− compared to wild type mice (P = 0.0524, unpaired t-test), with greatest reductions in hippocampus (P = 0.0062, 2-way ANOVA with Sidak’s post hoc test). Influx of 70 kD tracer was reduced to a greater extent, with greatest declines in hippocampus and diencephalon (P = 0.0004, P = 0.0065, respectively, 2-way ANOVA with Sidak’s post hoc test). C Schematic outline of study evaluating impact of AQP4 localization on Aβ deposition in the Tg2576 line. At 6 months of age, soluble Aβ40 (D; P = 0.0022, unpaired t-test) and insoluble Aβ40 (E; P = 0.0277, unpaired t-test) were significantly increased in Tg2576 (+); SNTA1−/− compared to Tg2576 (+); SNTA1+/+ littermates. Soluble Aβ42 (F; P = 0.0022, unpaired t-test) levels were increased in Tg2576 (+); SNTA1−/− compared to Tg2576 (+); SNTA1+/+ littermates, although no significant change in insoluble Aβ42 was observed (G). D–G Regression analysis showed that reduced capillary-associated PV Endfoot AQP4 IF was associated with increasing soluble Aβ40 (PCapi = 0.0035, R2Capi = 0.4030), insoluble Aβ40 (PCapi = 0.0384, R2Capi = 0.2286), and soluble Aβ42 (PCapi = 0.0147, R2Capi = 0.3024). Reduced large vessel-associated PV Endfoot AQP4 IF was significantly associated with increasing soluble Aβ40 (PLG-Ves = 0.0013, R2LG-Ves = 0.4651) and soluble Aβ42 (PLG-Ves = 0.0015, R2LG-Ves = 0.4574)