FIGURE 5.

Reduced density of synaptic AMPARs in dendritic spines of APP/PS1 mice at 12 months. (A–F) Electron micrographs of the hippocampus showing immunoparticles for AMPARs at excitatory synaptic sites of dendritic spines of pyramidal cells in the CA1 stratum radiatum, as detected using the SDS-FRL technique. Postsynaptic membrane specializations (IMP clusters, pseudo colored in blue for wild type and in red for APP/PS1 to aid visualization) show strong immunoreactivity for AMPARs (10 nm gold particles) in the wild type, while they show weaker immunoreactivity in the APP/PS1. Scale bars: (A–F), 200 nm. (G) Scatter plots showing the correlation between surface areas of postsynaptic membrane specializations and numbers of gold particles labeling AMPARs in wild type and APP/PS1 mice. (H) Histograms showing the distribution of densities of gold particles that label AMPARs of individual postsynaptic membrane specializations in the hippocampal CA1 region in wild type and APP/PS1 mice. (I) Quantitative analysis showing mean densities of AMPARs in excitatory synapses in spines in wild type and APP/PS1 mice. A significant reduction in the densities of AMPAR immunoparticles were detected in dendritic spines of APP/PS1 mice (261 ± 13 immunoparticles/μm²) compared to age matched wild type (459 ± 16 immunoparticles/μm²) (Two-way ANOVA test and Bonferroni post-hoc test, p < 0.0001).