Figure 4.
Aggravation and segregation of Reelin and amyloid-β plaques pathology in the hippocampus and cortex of 9- and 15-month-old double mutant reln/app mice. A–I, Triple immunofluorescence stainings using Cy3-GFAP (red), anti-Aβ1-40/42 (green), and anti-Reelin (blue) antibodies on cortical (A–F) and hippocampal (G–I) brain sections of 9-month-old app (A–C) and reln/app mice (D–I). In the double mutants, amyloid-β plaques were densely surrounded and tightly associated with reactive astrocytes, whereas in app subjects only moderate astrogliosis was evident. Note the intense Reelin immunoreactivity associated with fibrillary amyloid-β plaques (B vs E, arrows) and their striking segregation from Aβ deposits (H, arrow) in the CA1 slm in reln/app compared with app subjects. J–O, Aggravation of the microgliosis and astrogliosis in reln/app mice at 15 months of age was particularly prominent in the entorhinal cortex (ECtx). Note the reduction in APP-expressing neurons in the aged double (N) versus single mutants (K). Scale bars: C, F, I, 10 μm; L, O, 20 μm.