Fig. 3.

Precise quantification of PSD loss using array tomography. Postsynaptic densities (PSD95; green), oligomeric Aβ (NAB61; red), plaque cores (ThioS; blue), and nuclei (DAPI; blue) were stained on ribbons of 70-nm sections of APP/PS1 and nontransgenic cortex (part of a single section from the APP/PS1 cortex shown in A and B). To quantify the relationship between synapse loss and proximity to a plaque, images were taken of the same area on serial sections, the volumes aligned, and PSD95 puncta density was analyzed. Volumes were chosen within the plaque core (box C in B), the halo of oligomeric Aβ surrounding the core (arrow in A, box H in B), and in volumes extending out from the edge of the halo in 10-μm increments. Quantification (C) reveals significant PSD loss compared with control cortex (dotted line shows control average, ANOVA PSD density-dependent variable, genotype-independent F_1,195 = 71.149, P < 0.0001). Density of PSDs also decreases in APP/PS1 cortex in areas near plaques (ANOVA synapse density-dependent variable, distance category independent split by genotype F_6,123 = 36.323, P < 0.0001; synapse density correlates with average distance from halo edge correlation coefficient 0.706, P < 0.0001). *, P < 0.05 ANOVA split by distance category comparison to control average. (Scale bar: 10 μm.)