Figure 2.
Synapse loss correlates with oligomeric amyloid-β at synapses. The burden of oligomeric amyloid-β in Alzheimer’s disease brain is highest around plaques and decreases exponentially to control levels (represented by dotted line) with increasing distance from the plaque (A). Three dimensional reconstructions of array tomograms (12 sections reconstructed in B) reveal that oligomeric amyloid-β associates with a subset of synapses in Alzheimer’s disease brain. (C) Enlargements of the reconstruction showing examples of opposed pre- and postsynapses with no oligomeric amyloid-β (left), an oligomeric amyloid-β positive presynaptic element (arrowhead) and an oligomeric amyloid-β positive postsynaptic element (arrow). The level of co-localization between NAB61-positive puncta and presynaptic (D) or postsynaptic elements (E) is highest near plaques in Alzheimer’s disease and decreases exponentially to reach normal levels at distances >50 µm away from plaques (Kruskal–Wallis test with distance from plaque independent variable, P < 0.05, *P < 0.05 Wilcoxon all pairs post hoc test compared with control level). In Alzheimer’s disease brains, presysnaptic elements are shrunken compared with control brains (F, *P < 0.05 Wilcoxon test) and there is a trend towards shrinkage of postsynaptic densities (P = 0.08) that becomes significant when only the volumes within 10 µm of a plaque edge are considered. The presence of NAB61 positive oligomeric amyloid-β puncta at synapses is associated with smaller postsynaptic densities in this same region near plaques in Alzheimer’s disease brains and in control brains (G). Synapsin I puncta volumes are not significantly affected by the presence of oligomeric amyloid-β although there is a trend towards presynapse shrinkage in Alzheimer’s disease brains. Scale bars: B = 5 µm; C = 2 µm. AD = Alzheimer’s disease.