Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.
Identifieur interne : 000005 ( PubMed/Curation ); précédent : 000004; suivant : 000006Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.
Auteurs : Daryl J. Wile [Canada] ; Pankaj A. Agarwal [Inde] ; Michael Schulzer [Canada] ; Edwin Mak [Canada] ; Katherine Dinelle [Canada] ; Elham Shahinfard [Canada] ; Nasim Vafai [Canada] ; Kazuko Hasegawa [Japon] ; Jing Zhang [États-Unis] ; Jessamyn Mckenzie [Canada] ; Nicole Neilson [Canada] ; Audrey Strongosky [États-Unis] ; Ryan J. Uitti [États-Unis] ; Mark Guttman [Canada] ; Cyrus P. Zabetian [États-Unis] ; Yu-Shin Ding [États-Unis] ; Mike Adam [Canada] ; Jan Aasly [Norvège] ; Zbigniew K. Wszolek [États-Unis] ; Matthew Farrer [Canada] ; Vesna Sossi [Canada] ; A Jon Stoessl [Canada]Source :
- The Lancet. Neurology [ 1474-4465 ] ; 2017.
English descriptors
- KwdEn :
- Adult, Aged, Brain (metabolism), Cross-Sectional Studies, Dihydroxyphenylalanine (analogs & derivatives), Dopamine Plasma Membrane Transport Proteins (metabolism), Female, Heterozygote, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (genetics), Male, Middle Aged, Mutation, Parkinson Disease (genetics), Parkinson Disease (metabolism), Positron-Emission Tomography (methods), Radiopharmaceuticals, Serotonin Plasma Membrane Transport Proteins (metabolism).
- MESH :
- chemical , analogs & derivatives : Dihydroxyphenylalanine.
- chemical , genetics : Leucine-Rich Repeat Serine-Threonine Protein Kinase-2.
- genetics : Parkinson Disease.
- metabolism : Brain, Dopamine Plasma Membrane Transport Proteins, Parkinson Disease, Serotonin Plasma Membrane Transport Proteins.
- methods : Positron-Emission Tomography.
- Adult, Aged, Cross-Sectional Studies, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Radiopharmaceuticals.
Abstract
People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes.
DOI: 10.1016/S1474-4422(17)30056-X
PubMed: 28336296
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.</title><author><name sortKey="Wile, Daryl J" sort="Wile, Daryl J" uniqKey="Wile D" first="Daryl J" last="Wile">Daryl J. Wile</name><affiliation wicri:level="1"><nlm:affiliation>University of British Columbia, Department of Medicine, Vancouver, BC, Canada. Electronic address: dwile@mail.ubc.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>University of British Columbia, Department of Medicine, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Agarwal, Pankaj A" sort="Agarwal, Pankaj A" uniqKey="Agarwal P" first="Pankaj A" last="Agarwal">Pankaj A. Agarwal</name><affiliation wicri:level="1"><nlm:affiliation>Global Hospitals, Mumbai, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Global Hospitals, Mumbai</wicri:regionArea></affiliation></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Statistics, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Statistics, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Dinelle, Katherine" sort="Dinelle, Katherine" uniqKey="Dinelle K" first="Katherine" last="Dinelle">Katherine Dinelle</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Shahinfard, Elham" sort="Shahinfard, Elham" uniqKey="Shahinfard E" first="Elham" last="Shahinfard">Elham Shahinfard</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Vafai, Nasim" sort="Vafai, Nasim" uniqKey="Vafai N" first="Nasim" last="Vafai">Nasim Vafai</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Hasegawa, Kazuko" sort="Hasegawa, Kazuko" uniqKey="Hasegawa K" first="Kazuko" last="Hasegawa">Kazuko Hasegawa</name><affiliation wicri:level="1"><nlm:affiliation>Sagamihara National Hospital, Sagamihara, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Sagamihara National Hospital, Sagamihara</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA</wicri:regionArea></affiliation></author><author><name sortKey="Mckenzie, Jessamyn" sort="Mckenzie, Jessamyn" uniqKey="Mckenzie J" first="Jessamyn" last="Mckenzie">Jessamyn Mckenzie</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Neilson, Nicole" sort="Neilson, Nicole" uniqKey="Neilson N" first="Nicole" last="Neilson">Nicole Neilson</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Strongosky, Audrey" sort="Strongosky, Audrey" uniqKey="Strongosky A" first="Audrey" last="Strongosky">Audrey Strongosky</name><affiliation wicri:level="1"><nlm:affiliation>Mayo Clinic, Jacksonville, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mayo Clinic, Jacksonville, FL</wicri:regionArea></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J" last="Uitti">Ryan J. Uitti</name><affiliation wicri:level="1"><nlm:affiliation>Mayo Clinic, Jacksonville, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mayo Clinic, Jacksonville, FL</wicri:regionArea></affiliation></author><author><name sortKey="Guttman, Mark" sort="Guttman, Mark" uniqKey="Guttman M" first="Mark" last="Guttman">Mark Guttman</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Movement Disorders, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Movement Disorders, Toronto, ON</wicri:regionArea></affiliation></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P" last="Zabetian">Cyrus P. Zabetian</name><affiliation wicri:level="1"><nlm:affiliation>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA</wicri:regionArea></affiliation></author><author><name sortKey="Ding, Yu Shin" sort="Ding, Yu Shin" uniqKey="Ding Y" first="Yu-Shin" last="Ding">Yu-Shin Ding</name><affiliation wicri:level="1"><nlm:affiliation>New York University School of Medicine, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>New York University School of Medicine, New York, NY</wicri:regionArea></affiliation></author><author><name sortKey="Adam, Mike" sort="Adam, Mike" uniqKey="Adam M" first="Mike" last="Adam">Mike Adam</name><affiliation wicri:level="1"><nlm:affiliation>TRIUMF, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>TRIUMF, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Aasly, Jan" sort="Aasly, Jan" uniqKey="Aasly J" first="Jan" last="Aasly">Jan Aasly</name><affiliation wicri:level="1"><nlm:affiliation>Norwegian University of Science and Technology, Trondheim, Norway.</nlm:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Norwegian University of Science and Technology, Trondheim</wicri:regionArea></affiliation></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K" last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="1"><nlm:affiliation>Mayo Clinic, Jacksonville, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mayo Clinic, Jacksonville, FL</wicri:regionArea></affiliation></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Genetics, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Genetics, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name><affiliation wicri:level="1"><nlm:affiliation>University of British Columbia, Department of Medicine, Vancouver, BC, Canada; Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>University of British Columbia, Department of Medicine, Vancouver, BC, Canada; Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28336296</idno><idno type="pmid">28336296</idno><idno type="doi">10.1016/S1474-4422(17)30056-X</idno><idno type="wicri:Area/PubMed/Corpus">000005</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000005</idno><idno type="wicri:Area/PubMed/Curation">000005</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000005</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.</title><author><name sortKey="Wile, Daryl J" sort="Wile, Daryl J" uniqKey="Wile D" first="Daryl J" last="Wile">Daryl J. Wile</name><affiliation wicri:level="1"><nlm:affiliation>University of British Columbia, Department of Medicine, Vancouver, BC, Canada. Electronic address: dwile@mail.ubc.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>University of British Columbia, Department of Medicine, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Agarwal, Pankaj A" sort="Agarwal, Pankaj A" uniqKey="Agarwal P" first="Pankaj A" last="Agarwal">Pankaj A. Agarwal</name><affiliation wicri:level="1"><nlm:affiliation>Global Hospitals, Mumbai, India.</nlm:affiliation><country xml:lang="fr">Inde</country><wicri:regionArea>Global Hospitals, Mumbai</wicri:regionArea></affiliation></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Statistics, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Statistics, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Dinelle, Katherine" sort="Dinelle, Katherine" uniqKey="Dinelle K" first="Katherine" last="Dinelle">Katherine Dinelle</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Shahinfard, Elham" sort="Shahinfard, Elham" uniqKey="Shahinfard E" first="Elham" last="Shahinfard">Elham Shahinfard</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Vafai, Nasim" sort="Vafai, Nasim" uniqKey="Vafai N" first="Nasim" last="Vafai">Nasim Vafai</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Hasegawa, Kazuko" sort="Hasegawa, Kazuko" uniqKey="Hasegawa K" first="Kazuko" last="Hasegawa">Kazuko Hasegawa</name><affiliation wicri:level="1"><nlm:affiliation>Sagamihara National Hospital, Sagamihara, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Sagamihara National Hospital, Sagamihara</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA</wicri:regionArea></affiliation></author><author><name sortKey="Mckenzie, Jessamyn" sort="Mckenzie, Jessamyn" uniqKey="Mckenzie J" first="Jessamyn" last="Mckenzie">Jessamyn Mckenzie</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Neilson, Nicole" sort="Neilson, Nicole" uniqKey="Neilson N" first="Nicole" last="Neilson">Nicole Neilson</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Strongosky, Audrey" sort="Strongosky, Audrey" uniqKey="Strongosky A" first="Audrey" last="Strongosky">Audrey Strongosky</name><affiliation wicri:level="1"><nlm:affiliation>Mayo Clinic, Jacksonville, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mayo Clinic, Jacksonville, FL</wicri:regionArea></affiliation></author><author><name sortKey="Uitti, Ryan J" sort="Uitti, Ryan J" uniqKey="Uitti R" first="Ryan J" last="Uitti">Ryan J. Uitti</name><affiliation wicri:level="1"><nlm:affiliation>Mayo Clinic, Jacksonville, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mayo Clinic, Jacksonville, FL</wicri:regionArea></affiliation></author><author><name sortKey="Guttman, Mark" sort="Guttman, Mark" uniqKey="Guttman M" first="Mark" last="Guttman">Mark Guttman</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Movement Disorders, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Movement Disorders, Toronto, ON</wicri:regionArea></affiliation></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P" last="Zabetian">Cyrus P. Zabetian</name><affiliation wicri:level="1"><nlm:affiliation>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA</wicri:regionArea></affiliation></author><author><name sortKey="Ding, Yu Shin" sort="Ding, Yu Shin" uniqKey="Ding Y" first="Yu-Shin" last="Ding">Yu-Shin Ding</name><affiliation wicri:level="1"><nlm:affiliation>New York University School of Medicine, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>New York University School of Medicine, New York, NY</wicri:regionArea></affiliation></author><author><name sortKey="Adam, Mike" sort="Adam, Mike" uniqKey="Adam M" first="Mike" last="Adam">Mike Adam</name><affiliation wicri:level="1"><nlm:affiliation>TRIUMF, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>TRIUMF, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Aasly, Jan" sort="Aasly, Jan" uniqKey="Aasly J" first="Jan" last="Aasly">Jan Aasly</name><affiliation wicri:level="1"><nlm:affiliation>Norwegian University of Science and Technology, Trondheim, Norway.</nlm:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Norwegian University of Science and Technology, Trondheim</wicri:regionArea></affiliation></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K" last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="1"><nlm:affiliation>Mayo Clinic, Jacksonville, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Mayo Clinic, Jacksonville, FL</wicri:regionArea></affiliation></author><author><name sortKey="Farrer, Matthew" sort="Farrer, Matthew" uniqKey="Farrer M" first="Matthew" last="Farrer">Matthew Farrer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Genetics, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Genetics, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics and Astronomy, Vancouver, BC</wicri:regionArea></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name><affiliation wicri:level="1"><nlm:affiliation>University of British Columbia, Department of Medicine, Vancouver, BC, Canada; Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>University of British Columbia, Department of Medicine, Vancouver, BC, Canada; Pacific Parkinson's Research Centre, Vancouver, BC</wicri:regionArea></affiliation></author></analytic><series><title level="j">The Lancet. Neurology</title><idno type="eISSN">1474-4465</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Brain (metabolism)</term><term>Cross-Sectional Studies</term><term>Dihydroxyphenylalanine (analogs & derivatives)</term><term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term><term>Female</term><term>Heterozygote</term><term>Humans</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (genetics)</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Positron-Emission Tomography (methods)</term><term>Radiopharmaceuticals</term><term>Serotonin Plasma Membrane Transport Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Dihydroxyphenylalanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Parkinson Disease</term><term>Serotonin Plasma Membrane Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Positron-Emission Tomography</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Cross-Sectional Studies</term><term>Female</term><term>Heterozygote</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Mutation</term><term>Radiopharmaceuticals</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28336296</PMID><DateCreated><Year>2017</Year><Month>03</Month><Day>24</Day></DateCreated><DateCompleted><Year>2017</Year><Month>04</Month><Day>20</Day></DateCompleted><DateRevised><Year>2017</Year><Month>04</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1474-4465</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>5</Issue><PubDate><Year>2017</Year><Month>May</Month></PubDate></JournalIssue><Title>The Lancet. Neurology</Title><ISOAbbreviation>Lancet Neurol</ISOAbbreviation></Journal><ArticleTitle>Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.</ArticleTitle><Pagination><MedlinePgn>351-359</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1474-4422(17)30056-X</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/S1474-4422(17)30056-X</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson's disease, people with sporadic Parkinson's disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson's disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson's Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson's disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage ((18)F-6-fluoro-L-dopa; (18)F-FDOPA). We compared findings with those in people with sporadic Parkinson's disease and age-matched healthy controls. In the second study, distinct groups of LRRK2 mutation carriers, individuals with sporadic Parkinson's disease, and age-matched healthy controls seen from November, 2012, to May, 2016, were studied with tracers for the serotonin transporter and vesicular monoamine transporter 2 (VMAT2). Striatal dopamine transporter binding, VMAT2 binding, (18)F-FDOPA uptake, and serotonin transporter binding in multiple brain regions were compared by ANCOVA, adjusted for age.</AbstractText><AbstractText Label="FINDINGS" NlmCategory="RESULTS">Between January, 1997, and January, 2012, we obtained data for our first study from 40 LRRK2 mutation carriers, 63 individuals with sporadic Parkinson's disease, and 35 healthy controls. We identified significant group differences in striatal dopamine transporter binding (all age ranges in caudate and putamen, p<0·0001) and (18)F-FDOPA uptake (in caudate: age ≤50 years, p=0·0002; all other age ranges, p<0·0001; in putamen: all age ranges, p<0·0001). LRRK2 mutation carriers with manifest Parkinson's disease (n=15) had reduced striatal dopamine transporter binding and (18)F-FDOPA uptake, comparable with amounts seen in individuals with sporadic Parkinson's disease of similar duration. LRRK2 mutation carriers without manifest Parkinson's disease (n=25) had greater (18)F-FDOPA uptake and dopamine transporter binding than did individuals with sporadic Parkinson's disease, with (18)F-FDOPA uptake comparable with controls and dopamine transporter binding lower than in controls. Between November, 2012, and May, 2016, we obtained data for our second study from 16 LRRK2 mutation carriers, 13 individuals with sporadic Parkinson's disease, and nine healthy controls. Nine LRRK2 mutation carriers without manifest Parkinson's disease had significantly elevated serotonin transporter binding in the hypothalamus (compared with controls, individuals with LRRK2 Parkinson's disease, and people with sporadic Parkinson's disease, p<0·0001), striatum (compared with people with sporadic Parkinson's disease, p=0·02), and brainstem (compared with LRRK2 mutation carriers with manifest Parkinson's disease, p=0·01), after adjustment for age. Serotonin transporter binding in the cortex did not differ significantly between groups after age adjustment. Striatal VMAT2 binding was reduced in all individuals with manifest Parkinson's disease and reduced asymmetrically in one LRRK2 mutation carrier without manifest disease.</AbstractText><AbstractText Label="INTERPRETATION" NlmCategory="CONCLUSIONS">Dopaminergic and serotonergic changes progress in a similar fashion in LRRK2 mutation carriers with manifest Parkinson's disease and individuals with sporadic Parkinson's disease, but LRRK2 mutation carriers without manifest Parkinson's disease show increased serotonin transporter binding in the striatum, brainstem, and hypothalamus, possibly reflecting compensatory changes in serotonergic innervation preceding the motor onset of Parkinson's disease. Increased serotonergic innervation might contribute to clinical differences in LRRK2 Parkinson's disease, including the emergence of non-motor symptoms and, potentially, differences in the long-term response to levodopa.</AbstractText><AbstractText Label="FUNDING" NlmCategory="BACKGROUND">Canada Research Chairs, Michael J Fox Foundation, National Institutes of Health, Pacific Alzheimer Research Foundation, Pacific Parkinson's Research Institute, National Research Council of Canada.</AbstractText><CopyrightInformation>Copyright © 2017 Elsevier Ltd. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wile</LastName><ForeName>Daryl J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>University of British Columbia, Department of Medicine, Vancouver, BC, Canada. Electronic address: dwile@mail.ubc.ca.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Agarwal</LastName><ForeName>Pankaj A</ForeName><Initials>PA</Initials><AffiliationInfo><Affiliation>Global Hospitals, Mumbai, India.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schulzer</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Statistics, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mak</LastName><ForeName>Edwin</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dinelle</LastName><ForeName>Katherine</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shahinfard</LastName><ForeName>Elham</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vafai</LastName><ForeName>Nasim</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hasegawa</LastName><ForeName>Kazuko</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Sagamihara National Hospital, Sagamihara, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McKenzie</LastName><ForeName>Jessamyn</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Neilson</LastName><ForeName>Nicole</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Strongosky</LastName><ForeName>Audrey</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Mayo Clinic, Jacksonville, FL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uitti</LastName><ForeName>Ryan J</ForeName><Initials>RJ</Initials><AffiliationInfo><Affiliation>Mayo Clinic, Jacksonville, FL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guttman</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Centre for Movement Disorders, Toronto, ON, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zabetian</LastName><ForeName>Cyrus P</ForeName><Initials>CP</Initials><AffiliationInfo><Affiliation>Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, WA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ding</LastName><ForeName>Yu-Shin</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>New York University School of Medicine, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Adam</LastName><ForeName>Mike</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>TRIUMF, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aasly</LastName><ForeName>Jan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Norwegian University of Science and Technology, Trondheim, Norway.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wszolek</LastName><ForeName>Zbigniew K</ForeName><Initials>ZK</Initials><AffiliationInfo><Affiliation>Mayo Clinic, Jacksonville, FL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Farrer</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sossi</LastName><ForeName>Vesna</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Physics and Astronomy, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stoessl</LastName><ForeName>A Jon</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>University of British Columbia, Department of Medicine, Vancouver, BC, Canada; Pacific Parkinson's Research Centre, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>03</Month><Day>20</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Lancet Neurol</MedlineTA><NlmUniqueID>101139309</NlmUniqueID><ISSNLinking>1474-4422</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050483">Dopamine Plasma Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019275">Radiopharmaceuticals</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050486">Serotonin Plasma Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>2C598205QX</RegistryNumber><NameOfSubstance UI="C043437">fluorodopa F 18</NameOfSubstance></Chemical><Chemical><RegistryNumber>63-84-3</RegistryNumber><NameOfSubstance UI="D004295">Dihydroxyphenylalanine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C495280">LRRK2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000071158">Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003430" MajorTopicYN="N">Cross-Sectional 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MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D049268" MajorTopicYN="N">Positron-Emission Tomography</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019275" MajorTopicYN="N">Radiopharmaceuticals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050486" MajorTopicYN="N">Serotonin Plasma Membrane Transport Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>07</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2017</Year><Month>01</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>02</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>3</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>4</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>3</Month><Day>25</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28336296</ArticleId><ArticleId IdType="pii">S1474-4422(17)30056-X</ArticleId><ArticleId 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