18F-AV133 Cerebral VMAT2 Binding Correlated with α-synuclein Spliced Variants in Parkinson’s Disease

Rui Gao, Guangjian Zhang, Xueqi Chen, Savina Reid and Yun Zhou

Abstract

The study was designed to evaluate the connections between genotyping and functional image-based phenotyping in Parkinson’s disease (PD). The associations between18F-AV133 cerebral vesicular monoamine transporter 2 (VMAT2) binding and α-synuclein gene (SNCA) spliced variants were studied within the Parkinson’s Progression Markers Initiative study (PPMI) project. 18F-AV133 PET, structural magnetic resonance imaging (MRI), clinical assessments, and α-synuclein isoform data for 22 PD patients and 4 controls were collected from the PPMI project. Eight out of the 22 PD patients undertaken 18F-AV133 PET were presented with SNCA transcript measurements. The 18F-AV133 cerebral standardized uptake value ratio (SUVR) relative to the occipital cortex was calculated as an index of VMAT2 density. The differential expression of 5 SNCA transcript variants (the transcript with boundaries (E3E4), lack exon 5 (E4E6), specifically with a long 3’UTR region (3UTR1 and 3UTR2), and only comprises exons 1-4 (007)) was ascertained by the use of isoform-specific primers and a high-precision Nano String gene expression assay. Region of interest (ROI)- and voxel-wise-based statistical analysis were performed using statistical parametric mapping software (SPM8). In contrast to controls, the highest reduction of 18FAV133 SUVRs was found in left (contralateral to the predominantly affected side at onset) posterior putamen (54.1%), followed by right posterior putamen (43.2%), left anterior putamen (35.6%), right anterior putamen (27.9%), caudate (22.7%) (p < 0.01).The predominantly affected side at onset was right for seven out of the eight PD patients. There were significant correlations between ROI SUVRs and SNCA transcript variants: left anterior putamen with SNCA-007 (Pearson r = 0.85, p < 0.01); left anterior putamen with SNCA-E4E6 (r = 0.77, p = 0.03); left caudate with SNCA-E3E4 (r = 0.72, p = 0.04); and left ventral striatum with SNCA-E3E4 (r = 0.85, p < 0.01). Voxel-wise analysis showed that the left sub-lobar and anterior putamen were correlated with SNCA-007, and the left subcallosal gyrus and ventral striatum were significantly correlated with SNCA-E3E4 (p < 0.001). The initial results demonstrated a connection between SNCA splice variants in blood and monoaminergic degenerations in PD measured by 18F-AV133 PET.

Published on: January 12, 2016
doi: 10.17756/jnpn.2016-002
Citation:  Gao R, Zhang G, Chen X, Reid S, Zhou Y. 2016. 18F-AV133 Cerebral VMAT2 Binding Correlated with α-synuclein Spliced Variants in Parkinson’s Disease. J Neuroimaging Psychiatry Neurol 1(1): 4-9.

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