FIGURE 5.

Hippocampal synaptic vesicle density (SVD) decreases in the remaining presynaptic terminals surrounding Aβ deposits. (A–C) With the aim of quantifying the SVD at 4.5 months of age, we selected presynaptic terminals with a minimum size (rectangles, 0.5 μm²), and manually counted the synaptic vesicles located within that area, close to the postsynaptic density (postsynaptic element in green). Here, some examples of presynaptic terminals with a very high (A), medium-high (B), and low (C) vesicular densities are shown. Note that low SVD was usually accompanied by autophagic vesicles build-up, as shown in panel (C). (D) Control mice displayed the most elevated ratio of high/intermediate SVDs, which was very similar to the densities from interplaque locations in the double transgenic mice (APP/PS1ip). Periplaque areas (APP/PS1p) exhibited a lower ratio of dense synapses, and synapses with a very low density (<10 vesicles/μm²) were detected. Kruskal–Wallis ANOVA, 11 degrees of freedom; H = 65.46, p < 0.001; Dunn test. *p < 0.05; ***p < 0.001. APP/PS1p vs. control: ◆p < 0.001. (E) Synapses that were located closer to the plaques displayed less vesicle density. Kruskal–Wallis ANOVA, 11 degrees of freedom; H = 27.36, p = 0.004; Dunn test: *p < 0.017. Scale bars, (A–C) 200 nm.