To test the hypothesis that the change in synapse size in the AD material might be the result of a preferential loss of small synapses from the neuropil, frequency histograms were constructed of synapse size in both the middle and superior temporal gyrus61. The shape of the histograms was very similar between both the AD and control subjects, with the exception that in AD the central location of synapse size was skewed to the right, suggesting that the change occurred throughout the entire distribution of synapses and that the loss was not targeted toward smaller synapses. Since the AD and nondemented controls were both age and PMI matched, the overall increase in apposition size in the AD group is most likely disease related. Other than a change in the size of the apposition length, the synapses in both the AD and non-demented control tissue appeared identical with approximately the same packing density of synaptic vesicles. Possible functional importance of this change in synapse size has been a topic of speculation and may relate to the brain's attempt at maintaining a certain amount of total synaptic contact area81.

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