Fig. 3

LRP1 genetic deletion from pericytes inhibits Cy3-Aβ42 uptake by pericytes in mouse brain slices. a Diagram illustrating generation of Lrp1^lox/lox; Cspg4-Cre mice by crossing Lrp1^lox/lox mice with Cspg4-Cre mice. b Representative high magnification images showing LRP1 expression in CD13+ pericytes on isolated murine brain capillaries from control Lrp1^lox/lox mice, but not Lrp1^lox/lox; Cspg4-Cre mice with LRP1 deletion from pericytes. Asterisks show LRP1 immunostaining in CD13+ pericytes in control Lrp1^lox/lox mice; arrow shows loss of LRP1 immunoreactivity in Lrp1^lox/lox; Cspg4-Cre mice. Scale bar: 5 μm. c Representative images showing Cy3-Aβ42 internalization by CD13+ pericytes in brain slices from control Lrp1^lox/lox mice, and a substantial loss of Cy3-Aβ42 uptake by pericytes in Lrp1^lox/lox; Cspg4-Cre mice. Asterisks show colocalization between Cy3-Aβ42 and CD13 signals. Scale bar: 25 μm. d High magnification images showing greatly reduced Cy3-Aβ42 internalization by a CD13+ pericyte on brain slices from Lrp1^lox/lox; Cspg4-Cre mice, in contrast to Aβ uptake by lectin-positive endothelial cells. Arrow points to pericyte lacking Cy3-Aβ42 signal. Scale bar: 5 μm. e, f Quantification of Cy3-Aβ42 cellular uptake by CD13+ pericytes (e) compared to all other CD13- (negative) brain cells (f) in brain slices from control Lrp1 ^lox/lox and Lrp1 ^lox/lox; Cspg4-Cre mice. N = 3 mice per group; mean ± s.e.m.; NS, not significant, p < 0.05 by Student’s t-test