Fig. 4

ApoE is cleared from brain along perivascular pathways a Low magnification image showing the distribution of intracisternally injected apoE3-647 and cascade blue (10 kDa) in brain 15 min after their injection (5 μL at 1 μL/min). b-d Magnified images of the boxed area in (panel a). e Magnified images of the boxed area in (panel d). f-h Cross section of a cortical penetrating artery showing the perivascular flow of apoE3-647 and cascade blue. i Intensity graph of the various fluorescent markers across the white line drawn in (panel h). j-l Presence of apoE3-647 and cascade blue in a representative cortical capillary 60 min after intraparenchymal injection (caudate nucleus, 0.5 μL at 0.1 μL/min). m-n Presence of apoE3-647 and cascade blue in a representative deep cerebral parenchymal vein 60 min after intraparenchymal injection (caudate nucleus). Intracisternal apoE3-647 (magenta) and cascade blue (blue) entered brain via the penetrating cortical arterial vessels (red) and distributed within the parenchyma. Panels a-h are images after intracisternal injection of apoE3-647 and cascade blue in NG2-DsRed reporter mice. Lectin-FITC was injected intravascularly to identify vessels. Panels j-n are images after intraparenchymal (caudate nucleus) injection of apoE3-647 and cascade blue in NG2-DsRed reporter mice. Scale bars: A = 100 μm, B-D = 50 μm, E-H and J-N =10 μm. PVS = perivascular space