Figure 6

Synapse density, synaptic ProSAP2/Shank3 and intracellular Zn²⁺ levels are decreased in APP-PS1 mouse brain sections. A) Cellular Zn²⁺ levels are reduced in APP-PS1 hippocampus. Hippocampal sections from WT and APP-PS1 mice were double stained with DAPI to reveal cell nuclei and Zinpyr-1 to fluorescent-detect intracellular Zn²⁺ (see Figure S6). The ratio of mean Zinpyr-1 grey values between APP-PS1 and WT mouse sections at 3, 6 and 12 months of age is shown. The intracellular zinc concentration is significantly decreased in sections from 6 and 12 month-old mice (right panel). An enrichment of Zn²⁺-ions can be found colocalizing with extracellular Aβ plaques (arrow). B,C) The total number of synapses per optic field was measured and the ratio of mean number of synapses per optic field between APP-PS1 and WT mice is shown. A significant decrease is visible at 12 months. B,D) Sections of APP-PS1 and WT mice were stained with anti-Bassoon or anti-VGluT antibody as presynaptic marker and ProSAP2/Shank3 or Shank1 antibodies, respectively. The mean signal intensity of Alexa568 labeled ProSAP/Shank proteins opposed to a Bassoon or VGluT signal was measured and the ratio of mean grey values between APP-PS1 and WT mice is shown (merged images in B include DAPI staining (blue)).