ApoE4-Driven Accumulation of Intraneuronal Oligomerized Aβ42 following Activation of the Amyloid Cascade In Vivo Is Mediated by a Gain of Function
Figure 1
The effects of apoE3, apoE4, and apoE deficiency on the levels of Aβ42 and oligomerized Aβ42 in CA1 hippocampal neurons following inhibition of neprilysin. ApoE3, apoE4, and apoE-deficient male mice were injected i.c.v. with the neprilysin inhibitor thiorphan or sham-treated for 7 days, after which their brains were excised and subjected to anti-Aβ42 and anti-I-11 immunofluorescence, as described in “Materials and Methods.” (a) Representative coronal sections of sham- and thiorphan-treated apoE-deficient mice (upper row) and thiorphan-treated apoE3 and apoE4 mice (lower row) immunostained with anti-Aβ42 are shown on the left ( μm). Quantification of the density of Aβ42 staining (; mice/group in the sham- and thiorphan-treated groups) in the CA1 neurons of the indicated mice is shown on the right. for the effects of treatment on the three mouse groups by one-way ANOVA. (b) Representative confocal images of I-11 of the CA1 area of the indicated mouse groups treated for 7 days with thiorphan (left) and quantification (right) of the density of I-11 staining (; mice/group in the sham- and thiorphan-treated groups) (; ). for the effect of treatment on the three mouse groups by one-way ANOVA. (c) Representative masked oligo-Aβ42 images of the CA1 area of the indicated mouse groups treated for 7 days with thiorphan (left) and quantification (right) of the density of oligo-Aβ42 staining (; mice/group in the sham- and thiorphan-treated groups). for the effect of treatment on the three mouse groups by one-way ANOVA.
