Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: The objective of this study was to investigate whether SV2A and/or VGLUT1 are suitable as markers for synaptic degeneration in neurodegenerative disorders and could potentially be used in the future for monitoring synaptic degeneration in vivo using positron emission tomography (PET).
Background: Synaptic degeneration is an early hallmark in neurodegenerative disorders and closely correlates with cognitive decline, and are thus likely to be suitable as progression and/or surrogate markers. A PET ligand for synaptic vesicle glycoprotein 2A (SV2A), has recently been developed. In order to evaluate whether this ligand could be used to monitor synaptic degeneration, potential changes in the protein levels of SV2A in brain tissue from patients with different neurodegenerative disorders needs to be determined. Another potential biomarker for specific synaptic degeneration is the vesicular glutamate transporter 1 (VGLUT1) given the prominent glutamatergic dysfunction and excitotoxicity inn neurodegenerative disorders.
Methods: Tissue from frontal cortex (BA9), cingulate cortex (BA24) and parietal cortex (BA40) from Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB) and Alzheimer’s disease (AD) patients as well as healthy controls (total n= 92) was obtained from Brains for Dementia Research, UK and homogenized. Levels of SV2A and GLUT1 were determined by using western blotting and ELISA. The identity of an additional SV2A band was determined by using immunoprecipitation and liquid chromatography tandem mass spectrometry (LC-MS/MS).
Results: Preliminary results show variable protein expression of SV2A and GLUT1 in all patient groups. Interestingly, apart from the expected band at 80 kD, and additional band was detected at approximately 45 kD in the samples with the least intense 80 kD band. The identity of this band is under investigation.
Conclusions: Analysis of more samples is needed in order to determine whether SV2A and VGLUT1 are suitable biomarkers for PD, DLB or AD. The increase of the 45 kD SV2A band contaminant with the decrease of the 80 kD band suggest that a truncated form of SV2A exist.
To cite this abstract in AMA style:
S. Frykman, M. Oosterhof, M.S. Ahmed, D. Howlet, T. Hortobagyi, P. Francis, D. Årsland. Protein levels of SV2A and VGLUT1 in brain tissue from patients with Parkinson’s disease, dementia with Lewy bodies and Alzheimer’s disease [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/protein-levels-of-sv2a-and-vglut1-in-brain-tissue-from-patients-with-parkinsons-disease-dementia-with-lewy-bodies-and-alzheimers-disease/. Accessed November 21, 2024.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/protein-levels-of-sv2a-and-vglut1-in-brain-tissue-from-patients-with-parkinsons-disease-dementia-with-lewy-bodies-and-alzheimers-disease/