Synaptic contact number and size in stratum radiatum CA1 of APP/PS1DeltaE9 transgenic mice.

Synaptic changes occur early in the course of Alzheimer's disease and are key to understanding the initial events in associated neurodegenerative processes. The quantitative analysis of synaptic morphology in transgenic mouse models of Alzheimer's disease can provide important insights into these processes. To this end, the total number and the distribution of the diameters of synaptic contacts in the stratum radiatum of the CA1 region of the hippocampus of 12-month-old APP/PS1DeltaE9 transgenic mice and wild type littermates have been evaluated by applying design-based stereological methods to material prepared for electron microscopy. Although there were no differences in the size of the synaptic contacts, the total number of synaptic contacts was significantly larger in the transgenic mice, suggesting that the transgenic effect at this age is synaptotrophic and that the presence of amyloid plaques and an elevated Abeta42/40 ratio are not necessarily detrimental to populations of synapses. The potential of this type of data in evaluating synaptic changes related to Alzheimer's disease is discussed and the methodology described in detail.