Microglial activation in Parkinson’s disease using [18F]-FEPPA
Identifieur interne : 000063 ( Main/Exploration ); précédent : 000062; suivant : 000064Microglial activation in Parkinson’s disease using [18F]-FEPPA
Auteurs : Christine Ghadery [Canada] ; Yuko Koshimori [Canada] ; Sarah Coakeley [Canada] ; Madeleine Harris [Canada] ; Pablo Rusjan [Canada] ; Jinhee Kim [Canada] ; Sylvain Houle [Canada] ; Antonio P. Strafella [Canada]Source :
- Journal of Neuroinflammation [ 1742-2094 ] ; 2017.
Abstract
Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson’s disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo.
Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [18F]-FEPPA between PD patients and HC. FEPPA total distribution volume (
Our results revealed a significant main effect of genotype on [18F]-FEPPA
Future investigations are needed to determine the significance of [18F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD.
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DOI: 10.1186/s12974-016-0778-1
PubMed: 28086916
PubMed Central: 5234135
Affiliations:
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of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Koshimori, Yuko" sort="Koshimori, Yuko" uniqKey="Koshimori Y" first="Yuko" last="Koshimori">Yuko Koshimori</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Coakeley, Sarah" sort="Coakeley, Sarah" uniqKey="Coakeley S" first="Sarah" last="Coakeley">Sarah Coakeley</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Harris, Madeleine" sort="Harris, Madeleine" uniqKey="Harris M" first="Madeleine" last="Harris">Madeleine Harris</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Neurology Division, Department of Medicine, Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Neurology Division, Department of Medicine, Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation wicri:level="4"><nlm:aff id="Aff2">Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation wicri:level="4"><nlm:aff id="Aff1">Neurology Division, Department of Medicine, Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Neurology Division, Department of Medicine, Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff2">Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff3">Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain, Imaging and Behaviour – Systems Neuroscience, Krembil Research Institute, UHN, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="Aff4">Toronto Western Hospital and Institute, CAMH-Research Imaging Centre, University of Toronto, Toronto, Ontario M5T 2S8 Canada</nlm:aff><orgName type="university">Université de Toronto</orgName><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author></analytic><series><title level="j">Journal of Neuroinflammation</title><idno type="eISSN">1742-2094</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Neuroinflammatory processes including activated microglia have been reported to play an important role in Parkinson’s disease (PD). Increased expression of translocator protein (TSPO) has been observed after brain injury and inflammation in neurodegenerative diseases. Positron emission tomography (PET) radioligand targeting TSPO allows for the quantification of neuroinflammation in vivo.</p></sec><sec><title>Methods</title><p>Based on the genotype of the rs6791 polymorphism in the TSPO gene, we included 25 mixed-affinity binders (MABs) (14 PD patients and 11 age-matched healthy controls (HC)) and 27 high-affinity binders (HABs) (16 PD patients and 11 age-matched HC) to assess regional differences in the second-generation radioligand [<sup>18</sup>F]-FEPPA between PD patients and HC. FEPPA total distribution volume (<italic>V</italic><sub>T</sub>) values in cortical as well as subcortical brain regions were derived from a two-tissue compartment model with arterial plasma as an input function.</p></sec><sec><title>Results</title><p>Our results revealed a significant main effect of genotype on [<sup>18</sup>F]-FEPPA <italic>V</italic><sub>T</sub> in every brain region, but no main effect of disease or disease × genotype interaction in any brain region. The overall percentage difference of the mean FEPPA <italic>V</italic><sub>T</sub> between HC-MABs and HC-HABs was 32.6% (SD = 2.09) and for PD-MABs and PD-HABs was 43.1% (SD = 1.21).</p></sec><sec><title>Conclusions</title><p>Future investigations are needed to determine the significance of [<sup>18</sup>F]-FEPPA as a biomarker of neuroinflammation as well as the importance of the rs6971 polymorphism and its clinical consequence in PD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tanner, Cm" uniqKey="Tanner C">CM Tanner</name></author><author><name sortKey="Goldman, Sm" uniqKey="Goldman S">SM Goldman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcgeer, Pl" uniqKey="Mcgeer P">PL McGeer</name></author><author><name sortKey="Itagaki, S" uniqKey="Itagaki S">S Itagaki</name></author><author><name sortKey="Boyes, Be" uniqKey="Boyes B">BE Boyes</name></author><author><name sortKey="Mcgeer, 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Suridjan</name></author><author><name sortKey="Rusjan, Pm" uniqKey="Rusjan P">PM Rusjan</name></author><author><name sortKey="Voineskos, An" uniqKey="Voineskos A">AN Voineskos</name></author><author><name sortKey="Selvanathan, T" uniqKey="Selvanathan T">T Selvanathan</name></author><author><name sortKey="Setiawan, E" uniqKey="Setiawan E">E Setiawan</name></author><author><name sortKey="Strafella, Ap" uniqKey="Strafella A">AP Strafella</name></author><author><name sortKey="Wilson, Aa" uniqKey="Wilson A">AA Wilson</name></author><author><name sortKey="Meyer, Jh" uniqKey="Meyer J">JH Meyer</name></author><author><name sortKey="Houle, S" uniqKey="Houle S">S Houle</name></author><author><name sortKey="Mizrahi, R" uniqKey="Mizrahi R">R Mizrahi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Ontario"><name sortKey="Ghadery, Christine" sort="Ghadery, Christine" uniqKey="Ghadery C" first="Christine" last="Ghadery">Christine Ghadery</name></region><name sortKey="Coakeley, Sarah" sort="Coakeley, Sarah" uniqKey="Coakeley S" first="Sarah" last="Coakeley">Sarah Coakeley</name><name sortKey="Coakeley, Sarah" sort="Coakeley, Sarah" uniqKey="Coakeley S" first="Sarah" last="Coakeley">Sarah Coakeley</name><name sortKey="Ghadery, Christine" sort="Ghadery, Christine" uniqKey="Ghadery C" first="Christine" last="Ghadery">Christine Ghadery</name><name sortKey="Harris, Madeleine" sort="Harris, Madeleine" uniqKey="Harris M" first="Madeleine" last="Harris">Madeleine Harris</name><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name><name sortKey="Kim, Jinhee" sort="Kim, Jinhee" uniqKey="Kim J" first="Jinhee" last="Kim">Jinhee Kim</name><name sortKey="Koshimori, Yuko" sort="Koshimori, Yuko" uniqKey="Koshimori Y" first="Yuko" last="Koshimori">Yuko Koshimori</name><name sortKey="Koshimori, Yuko" sort="Koshimori, Yuko" uniqKey="Koshimori Y" first="Yuko" last="Koshimori">Yuko Koshimori</name><name sortKey="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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