Figure 1.

P-glycoprotein (P-gp) expression was decreased in the brain capillaries of five familial Alzheimer's disease mutations (5XFAD) mice. (a and b) P-gp protein levels were measured by performing western blotting on total cerebral homogenates and cerebral capillaries that were isolated from the brains of wild-type and 5XFAD mice. β-Actin was used as a loading control. (c) Confocal microscopic analysis of P-gp and amyloid plaques in cortical sections (30 μm) from 6-month-old control and 5XFAD mice (n=3 for each). The amyloid plaques were labeled with the specific anti-amyloid-β peptide (Aβ) antibody (green; 4G8). P-gp (red) was clearly detected along the capillaries of the wild-type mice and far from the amyloid plaque deposits in 5XFAD mice (yellow arrow heads and the parts shown in the yellow dotted circles), but hardly detected near the amyloid plaque deposits in 5XFAD mice (the parts shown in the white dotted circles). Scale bars=10 and 30 μm. (d) Three-dimensional-structured illumination microscopy (3D-SIM) image of P-gp and amyloid plaques in the brains of wild-type and 5XFAD mice (n=3 for each). Amyloid plaques and P-gp were identified by the immunofluorescent detection of the 4G8 (green) and anti-P-gp antibody (red). Each panel shows different regions in the brains. The arrow heads indicate P-gp expression. Scale bar=2 μm