3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer's disease

The entorhinal cortex (EC) is especially vulnerable in the early stages of Alzheimers disease (AD). In particular, cognitive deficits have been linked to alterations in the upper layers of EC. In the present report, we examined layers II and III from eight human brain autopsies (four subjects with no recorded neurological alterations and four AD cases). We used stereological methods to assess cortical atrophy of the EC, and possible changes in the volume occupied by different cortical elements (neuronal and glial cell bodies; blood vessels; and neuropil). We performed 3D ultrastructural analyses of synapses using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to examine possible alterations related to AD. At the light microscope level, we found a significantly lower volume fraction occupied by neuronal bodies in layer III and a higher volume fraction occupied by glial cell bodies in layer II in AD cases. At the ultrastructural level we observed that (i) there was a significantly lower synaptic density in both layers in AD cases; (ii) synapses were larger and more complex in layer II in AD cases; and (iii) there was a greater proportion of small and simple synapses in layer III in AD cases than in control individuals. These structural differences may play a role in the anatomical basis for the impairment of cognitive functions in AD. Significant StatementAnalysis of the synaptic characteristics provides critical data on synaptic organization. Using 3D electron microscopy, the present study shows the synaptic organization of the neuropil of the human entorhinal cortex (EC) at the ultrastructural level. The EC is especially vulnerable in the early stages of Alzheimers disease (AD). Our present results show structural differences that may contribute as anatomical basis for the impairment of cognitive functions in AD. Thus, these results may help to understand the relationship between alterations of the synaptic circuits and the cognitive deterioration in AD.