Session Information
Date: Wednesday, June 22, 2016
Session Title: Parkinson's disease: Cognition
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: The aim of our study is to understand the role of synaptic dysfunction in cognitive decline by comparing the whole proteome of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), Alzheimer’s disease (AD) and non-demented postmortem brain tissues, employing both mass spectrometry based proteomics and immunoassay approaches.
Background: A significant decrease in cortical synapses has been previously reported in AD, which is more robustly correlated with cognitive decline than the classical AD pathologies. Less is known about its role in cognitive decline in PD and DLB.
Methods: Postmortem brain tissues from PD, DLB, AD and non-demented control cases (n=8 from each group) underwent mass spectrometry analyses. Approximately 800 synaptic proteins have been identified, and about 30 presented significantly altered levels among the dementia groups compared to controls. A handful of proteins have been chosen for further ELISA and Western blot analyses on a larger cohort of more than 80 postmortem brain samples from the above mentioned dementia groups.
Results: Preliminary analysis revealed decreased SNAP47 as well as synaptic vesicle 2C (SV2C) protein levels in PD and DLB. Also we have found decreased Gria 3 levels in AD cases compared to non-demented control cases. Cognition measured by the last MMSE score prior to death and rate of decline were associated with synaptic protein levels. Significant correlations between synaptic proteins with tangle and alpha-synuclein scores were also observed.
Conclusions: Several synaptic proteins are altered in PD, DLB, and AD versus controls. The role of synaptic proteins in blood or CSF as possible predictors of cognitive decline in Lewy body dementias and AD should be evaluated by further biomarker studies. Stabilization of synaptic protein levels may represent a novel treatment strategy in these diseases.
To cite this abstract in AMA style:
E. Bereczki, R.M.M. Branca, P.T. Francis, J.H. Baek, J. Lehtio, D. Aarsland. Synaptic biomarkers for cognitive decline in Lewy body dementias and Alzheimer’s disease. A mass spectrometry approach [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/synaptic-biomarkers-for-cognitive-decline-in-lewy-body-dementias-and-alzheimers-disease-a-mass-spectrometry-approach/. Accessed June 15, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/synaptic-biomarkers-for-cognitive-decline-in-lewy-body-dementias-and-alzheimers-disease-a-mass-spectrometry-approach/