Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Alisdair McNeill; 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

doi:10.1371/journal.pone.0069190

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

Alisdair McNeill, 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 LeesOswaldo Lorenzo-Betancor, Niccolo E. Mencacci, Pau Pastor, Sabina Pappata, Maria Teresa Pellecchia, Laura Silveria-Moriyama, Andrea Varrone, Tom Foltynie, Anthony H V Schapira

Neurology

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

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.

Original language	English (US)
Article number	e69190
Journal	PloS one
Volume	8
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0069190
State	Published - Jul 23 2013

Funding

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.

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10.1371/journal.pone.0069190

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McNeill, A., Wu, R. M., Tzen, K. Y., Aguiar, P. C., Arbelo, J. M., Barone, P., Bhatia, K., Barsottini, O., Bonifati, V., Bostantjopoulou, S., Bressan, R., Cossu, G., Cortelli, P., Felicio, A., Ferraz, H. B., Herrera, J., Houlden, H., Hoexter, M., Isla, C., ... Schapira, A. H. V. (2013). Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis. PloS one, 8(7), Article e69190. https://doi.org/10.1371/journal.pone.0069190

@article{ceacf19a03f843d2910deda3fccd15af,

title = "Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis",

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.",

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

note = "Funding Information: 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, Funda{\c c}{\~a}o Safra, Funda{\c c}{\~a}o 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. ",

year = "2013",

month = jul,

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doi = "10.1371/journal.pone.0069190",

language = "English (US)",

volume = "8",

journal = "PloS one",

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McNeill, A, Wu, RM, Tzen, KY, Aguiar, PC, Arbelo, JM, Barone, P, Bhatia, K, Barsottini, O, Bonifati, V, Bostantjopoulou, S, Bressan, R, Cossu, G, Cortelli, P, Felicio, A, Ferraz, HB, Herrera, J, Houlden, H, Hoexter, M, Isla, C, Lees, A, Lorenzo-Betancor, O, Mencacci, NE, Pastor, P, Pappata, S, Pellecchia, MT, Silveria-Moriyama, L, Varrone, A, Foltynie, T & Schapira, AHV 2013, 'Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis', PloS one, vol. 8, no. 7, e69190. https://doi.org/10.1371/journal.pone.0069190

TY - JOUR

T1 - Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease

T2 - Insights into Pathogenesis

AU - McNeill, Alisdair

AU - Wu, Ruey Meei

AU - Tzen, Kai Yuan

AU - Aguiar, Patricia C.

AU - Arbelo, Jose M.

AU - Barone, Paolo

AU - Bhatia, Kailash

AU - Barsottini, Orlando

AU - Bonifati, Vincenzo

AU - Bostantjopoulou, Sevasti

AU - Bressan, Rodrigo

AU - Cossu, Giovanni

AU - Cortelli, Pietro

AU - Felicio, Andre

AU - Ferraz, Henrique B.

AU - Herrera, Joanna

AU - Houlden, Henry

AU - Hoexter, Marcelo

AU - Isla, Concepcion

AU - Lees, Andrew

AU - Lorenzo-Betancor, Oswaldo

AU - Mencacci, Niccolo E.

AU - Pastor, Pau

AU - Pappata, Sabina

AU - Pellecchia, Maria Teresa

AU - Silveria-Moriyama, Laura

AU - Varrone, Andrea

AU - Foltynie, Tom

AU - Schapira, Anthony H V

N1 - Funding Information: 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.

PY - 2013/7/23

Y1 - 2013/7/23

N2 - 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.

AB - 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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U2 - 10.1371/journal.pone.0069190

DO - 10.1371/journal.pone.0069190

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JO - PloS one

JF - PloS one

IS - 7

M1 - e69190

ER -

Dopaminergic Neuronal Imaging in Genetic Parkinson's Disease: Insights into Pathogenesis

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