Quantification of oligomeric Aβ deposits and their association with PSDs. (A) The burden of oligomeric Aβ (percentage neuropil volume occupied by NAB61 staining) is increased in the APP/PS1 cortex compared with wild type (dotted line) (Mann–Whitney test P < 0.0001). The oligomeric Aβ burden also increases in volumes closer to plaques in APP/PS1 mice (Kruskal–Wallis test, distance-independent variable, split by genotype APP/PS1, P < 0.0001). (B) The percentage of excitatory synapses positive for oligomeric Aβ staining increases near plaques in the APP/PS1 trasngenic cortex (Kruskal–Wallis test, P < 0.0001). Post hoc tests show that the percentage of PSDs interacting with oligomeric Aβ is significantly higher than nontransgenic levels in the plaque core and halo, and there is a trend toward an increase between 0 and 10 μm away from the edge of the halo. (C) NAB61 deposits are larger in APP/PS1 mice than in wild-type cortex (Mann–Whitney test P < 0.0001), with very large deposits occurring, particularly in the halo (maximum size, 0.36 μm3). (D) A box plot of postsynaptic density size shows that PSDs are smaller in the APP/PS1 cortex than in nontransgenic cortex (Mann–Whitney test P < 0.0001), with a more substantial reduction in size in puncta associated with NAB61 deposits (Mann–Whitney test P = 0.0026). Even in nontransgenic brain, PSDs associated with oligomeric Aβ deposits are smaller than those not in contact with oligomeric Aβ (Mann–Whitney test P = 0.0243). Together, these data indicate that NAB61 interactions with the PSD may contribute to synapse loss. Data are not normally distributed and thus are presented as median with minima and maxima shown; control medians are dotted lines in A, B, and C. *, Post hoc Mann–Whitney tests P < 0.05; #, P = 0.06.