Extended Data Fig. 3: Expression of apoE4 compromises microglial barrier and phagocytic functions.
a, b, Brain sections from APP/iE3/CreER/+ (Ctrl, n = 18; TAM-induced, n = 16) or APP/iE4/CreER/+ mice (Ctrl, n = 19; TAM-induced, n = 21) at 9 months of age were immunostained with Iba1 antibody. The immunoreactivity of Iba1-positive microglia in cortex and hippocampus was quantified. Scale bar, 100 µm. c, d, TAM-induced APP/iE3/CreER/+ mice (n = 3) and APP/iE4/CreER/+ male mice (n = 4) at 9 months of age were subjected to 2-photon imaging. c, Representative images of GFP-positive microglia (green) and methoxy-X04-stained amyloid plaques (blue) monitored by two-photon in vivo imaging. Plaque associated microglia (number of microglia per 100 mm2; 1-3 fields/mouse) were quantified. Scale bar, 20 µm. *, P = 0.018. d, Representative images of microglial phagocytosis in APP/iE3/CreER/+ (n = 3) and APP/iE4/CreER/+ mice (n = 4) examined by two-photon imaging. The colocalization (pink) of microglia and Aβ are pseudo colored to illustrate the phagocytosed Aβ in microglia which was quantified. Scale bar, 50 µm. *, P = 0.032. a-d. Data represent mean ± s.e.m. N.S., not significant. Two-tailed, t-test.
