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. 2013 Jul 23;8(7):e69190.
doi: 10.1371/journal.pone.0069190. Print 2013.

Dopaminergic neuronal imaging in genetic Parkinson's disease: insights into pathogenesis

Alisdair McNeill  1 , Ruey-Meei Wu, Kai-Yuan Tzen, Patricia C Aguiar, Jose M Arbelo, Paolo Barone, Kailash Bhatia, Orlando Barsottini, Vincenzo Bonifati, Sevasti Bostantjopoulou, Rodrigo Bressan, Giovanni Cossu, Pietro Cortelli, Andre Felicio, Henrique B Ferraz, Joanna Herrera, Henry Houlden, Marcelo Hoexter, Concepcion Isla, Andrew Lees, Oswaldo Lorenzo-Betancor, Niccolo E Mencacci, Pau Pastor, Sabina Pappata, Maria Teresa Pellecchia, Laura Silveria-Moriyama, Andrea Varrone, Tom Foltynie, Anthony H V Schapira
Affiliations

Dopaminergic neuronal imaging in genetic Parkinson's disease: insights into pathogenesis

Alisdair McNeill et al. PLoS One. .

Abstract

Objectives: To compare the dopaminergic neuronal imaging features of different subtypes of genetic Parkinson's Disease.

Methods: A retrospective study of genetic Parkinson's diseases cases in which DaTSCAN (123I-FP-CIT) had been performed. Specific non-displaceable binding was calculated for bilateral caudate and putamen for each case. The right:left asymmetry index and striatal asymmetry index was calculated.

Results: Scans were available from 37 cases of monogenetic Parkinson's disease (7 glucocerebrosidase (GBA) mutations, 8 alpha-synuclein, 3 LRRK2, 7 PINK1, 12 Parkin). The asymmetry of radioligand uptake for Parkinson's disease with GBA or LRRK2 mutations was greater than that for Parkinson's disease with alpha synuclein, PINK1 or Parkin mutations.

Conclusions: The asymmetry of radioligand uptake in Parkinsons disease associated with GBA or LRRK2 mutations suggests that interactions with additional genetic or environmental factors may be associated with dopaminergic neuronal loss.

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Conflict of interest statement

Competing Interests: Below are the authors' declarations of funding sources, including commercial funders: Rueey-Mei Wu - Analysis of data, revising manuscript. Government research support National Science Council (96-2628-B-002-102-MY3), academic research support not attributed in manuscript National Science Council (98-2628-B-002-072-MY3) National Taiwan University Hospital (100-S1636), on editorial boards Parkinsonism and related disorders, Journal of Formosan Medical Association, Acta Neurologica Taiwanica and no conflicts of interest. Patricia Aguiar - Analysis and interpretation of data. Funding for travel from Roche, government research support FAPESP (grants 2010/19206-0; 2011/18202-3; 2011/14116-5, research grant from Edmond J Safra foundation and no conflicts of interest. Rodrigo Bressan - Analysis and interpretation of data. Research funding from Janssen, Eli Lily, Lundbeck, Novartis, Roche, FAPESP, CNPq, CAPES, Fundação Safra, Fundação ABADS. Shareholder in Radiopharmacus Ltda, Biomolecular Technology Ltda. Speaking fees from Astra Zeneca, Bristol, Janssen, Lundbeck, Roche. No conflicts of interest. Andre Felicio - Analysis and interpretation of data. funding for travel from Roche, Honoraria from Gerson Lehrman group, research funding from Parkinson's society Canada and no conflicts of interest. Henrique Ferraz - Analysis and interpretation of data. Funding for travel from Roche and Novartis and no conflicts of interest. Andrew Lees -Andrew Lees discloses financial support from the Reta Lila Weston Trust, University College London, Parkinson's UK and PSP Association. He is on the specialist board for Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira, Roche, has received consultancy fees from Genus, and honoraria from Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, BIAL, Noscira and Roche. Laura Silveria-Moriyama - Analysis and interpretation of data. Laura Silveira-Moriyama discloses financial support from the Reta Lila Weston Trust, University College London, University of Campinas, Parkinson's UK and Virginia Keiley Benefaction, and travels grants from UCB, Teva and Boehringer-Ingelheim. Tom Foltynie - Analysis and interpretation of data. Honoraria for speaking at meetings sponsored by St Jude medical, Abbott, Novartis. Grant support from Parkinson's UK, Cure Parkinson's Trust, the European Union and the Brain Research Trust. Anthony HV Schapira - Study design, analysis and interpretation of data, revising manuscript. Receives funding from the United Kingdom Medical Research Council, Wellcome Trust, Parkinson's UK and Kattan Trust. Specialist boards and educational symposia for Orion-Novartis, Teva-Lundbeck, Merck, BI, UCB. AH Schapira is an NIHR Senior Investigator. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Caudate and putament asymmetry index for subtypes of genetic Parkinson's disease.
1a. Boxplot of caudate asymmetry index for each genotype. Median caudate asymmetry is signficantly different for GBA compared to control. 1b. Boxplot of putamen asymmetry index for each genotype. Median putamen asymmetry is significantly different for GBA and LRRK2 groups compared to control.
Figure 2
Figure 2. Striatal asymmetry index by genotype.
The striatal asymmetry index was significantly higher for the GBA and LRRK2 genotypes (p<0.001). Graph shows mean SASI +/−1 standard error.
Figure 3
Figure 3. Representative DaTSCAN images.
3a. DaTscan from 50 year old man with GBA mutation, note predominantly right sided tracer loss. 3b. DaTscan from 67 year old woman with PINK1 mutation associated Parkinson's disease, note symmetrical loss of tracer uptake in caudate heads. 3c. DaTscan from 45 year old man with Parkin mutation associated Parkinson's disease and symmetrical loss of tracer uptake. 3d. DaTscan from 32 year old man with LRRK2 mutation, note asymmetrical loss of tracer uptake in caudate heads.
See this image and copyright information in PMC

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