Title: P1‐025: Altered expression of synaptic proteins in the neocortex of Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB)
Abstract: Neurodegenerative diseases are often characterized by synaptic dysfunction. In Alzheimer's Disease, significant down regulation of presynaptic proteins such as synaptotagmin, synaptophysin and GAP43 have been observed in frontal and entorhinal cortex whereas postsynaptic protein PSD95, is significantly increase in the frontal cortex. Here we aim to characterize synaptic changes in PDD and DLB patients and age-matched controls. Neocortical tissues from subjects (14 PDD, 13 DLB and 7 age-matched controls) were obtained from established longitudinal studies. Immunoblotting was performed on post-mortem brain tissue homogenates from the parahippocampus gyrus (Brodmann area 36) to measure pre and post synatic markers (synaptophysin, synaptotagmin, synapsin, Rabphilin 3A, syntaxin, SV2A, GAP 43 and PSD 95). Immunoblot densities were analyzed using one-way ANOVA with post-hoc Bonferroni correction. Results were considered statistically significant if p < 0.05. We found a significant reduction of synapsin, Rabphilin3A and synaptophysin in PDD (p = 0.030, 0.003 and 0.003 respectively) compared to control. Rabphilin 3A, synaptophysin and synaptotagmin were significantly reduced in DLB (p = 0.003, 0.035 and 0.004 respectively) compared to controls. No significant changes observed between PDD and DLB. SNARE complex, which is formed prior to neurotransmitter release, involved the specific docking of V-SNARE (Vesicle) and its respective targeted T-SNARE (Target). Interestingly, presynaptic proteins, that formed the V-SNARE (synaptotagmin, synapsin, synaptophysin) but not those involved in the T-SNARE (syntaxin) are significantly reduced in PDD and DLB. Significant down regulation of Rabphilin 3A, a GTPase which assists and regulates the efficiency of docking and matching of V-SNARE and T-SNARE is also observed in both PDD and DLB. These findings confirm a distinctive pattern of presynaptic changes which are likely linked to impairment of neurotransmitter release and points to further investigation of synaptic changes in various brain regions of PDD and DLB.
Publication Year: 2010
Publication Date: 2010-07-01
Language: en
Type: article
Indexed In: ['crossref']
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