Abstract
Frontotemporal lobe atrophy is a hallmark of Pick's disease (PiD), however, the underlying pathobiology of the neuronal losses is unknown. Synaptic losses have been described in Alzheimer's disease (AD) and correlate with the severity of dementia, however, few studies of synaptic integrity have been done to determine whether synaptic loss also contributes to symptoms in non-AD dementias. To begin to assess synaptic integrity in other types of dementia, we examined the site of termination of the hippocampal perforant pathway, the major source of afferent tracts to the hippocampus. We determined immunoreactivity for the synaptic-terminal specific protein synaptophysin in the outer molecular layer of the hippocampal dentate gyrus (OMDG) in eight PiD, nine AD, nine dementia with Lewy bodies (DLB), and seven control cases. Quantitative data were obtained using an Image-Pro automated image analysis system. In AD and PiD, synaptophysin immunoreactivity was visibly reduced in the OMDG. Densitometric analysis confirmed that there were statistically significant differences among groups in synaptophysin immunoreactivity when comparing the OMDG to the adjacent inner molecular layer of the hippocampal dentate gyrus (IMDG) (p = 0.002). These differences were present between PiD and both the control and DLB groups. The AD group also showed a reduction in synaptophysin immunoreactivity compared with DLB and control groups. In contrast, perforant pathway synaptic losses in DLB were minimal. Our data supports the hypothesis that focal synaptic losses occur in PiD and AD and may contribute to the cognitive deficits in both conditions.
Keywords: dementia, Pick's disease, synaptophysin, synapse
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