Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.
Identifieur interne : 000420 ( PubMed/Curation ); précédent : 000419; suivant : 000421Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.
Auteurs : Joseph J. Locascio [États-Unis] ; Shirley Eberly [États-Unis] ; Zhixiang Liao [États-Unis] ; Ganqiang Liu [États-Unis] ; Ashley N. Hoesing [États-Unis] ; Karen Duong [États-Unis] ; Ana Trisini-Lipsanopoulos [États-Unis] ; Kaltra Dhima [États-Unis] ; Albert Y. Hung [États-Unis] ; Alice W. Flaherty [États-Unis] ; Michael A. Schwarzschild [États-Unis] ; Michael T. Hayes [États-Unis] ; Anne-Marie Wills [États-Unis] ; U. Shivraj Sohur [États-Unis] ; Nicte I. Mejia [États-Unis] ; Dennis J. Selkoe [États-Unis] ; David Oakes [États-Unis] ; Ira Shoulson [États-Unis] ; Xianjun Dong [États-Unis] ; Ken Marek [États-Unis] ; Bin Zheng [États-Unis] ; Adrian Ivinson [États-Unis] ; Bradley T. Hyman [États-Unis] ; John H. Growdon [États-Unis] ; Lewis R. Sudarsky [États-Unis] ; Michael G. Schlossmacher [États-Unis] ; Bernard Ravina [Canada] ; Clemens R. Scherzer [États-Unis]Source :
- Brain : a journal of neurology [ 1460-2156 ] ; 2015.
English descriptors
- KwdEn :
- Aged, Cognition Disorders (etiology), Cognition Disorders (genetics), Dopamine Plasma Membrane Transport Proteins (metabolism), Female, Gene Expression Regulation, Genetic Testing, Humans, Male, Microarray Analysis, Middle Aged, Neuroimaging, Parkinson Disease (complications), Parkinson Disease (diagnostic imaging), Parkinson Disease (genetics), Parkinson Disease (pathology), RNA, Messenger (metabolism), Radionuclide Imaging, Severity of Illness Index, Tropanes, alpha-Synuclein (blood), alpha-Synuclein (genetics).
- MESH :
- chemical , blood : alpha-Synuclein.
- chemical , genetics : alpha-Synuclein.
- chemical , metabolism : Dopamine Plasma Membrane Transport Proteins, RNA, Messenger.
- complications : Parkinson Disease.
- diagnostic imaging : Parkinson Disease.
- etiology : Cognition Disorders.
- genetics : Cognition Disorders, Parkinson Disease.
- pathology : Parkinson Disease.
- Aged, Female, Gene Expression Regulation, Genetic Testing, Humans, Male, Microarray Analysis, Middle Aged, Neuroimaging, Radionuclide Imaging, Severity of Illness Index, Tropanes.
Abstract
There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.
DOI: 10.1093/brain/awv202
PubMed: 26220939
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Hyman</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Growdon, John H" sort="Growdon, John H" uniqKey="Growdon J" first="John H" last="Growdon">John H. Growdon</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Sudarsky, Lewis R" sort="Sudarsky, Lewis R" uniqKey="Sudarsky L" first="Lewis R" last="Sudarsky">Lewis R. Sudarsky</name><affiliation wicri:level="1"><nlm:affiliation>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G" last="Schlossmacher">Michael G. Schlossmacher</name><affiliation wicri:level="1"><nlm:affiliation>9 Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>9 Institute for Neurodegenerative Disorders, New Haven, CT 06510</wicri:regionArea></affiliation></author><author><name sortKey="Ravina, Bernard" sort="Ravina, Bernard" uniqKey="Ravina B" first="Bernard" last="Ravina">Bernard Ravina</name><affiliation wicri:level="1"><nlm:affiliation>10 Program in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1H8M5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>10 Program in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1H8M5</wicri:regionArea></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R" last="Scherzer">Clemens R. Scherzer</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA cscherzer@rics.bwh.harvard.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26220939</idno><idno type="pmid">26220939</idno><idno type="doi">10.1093/brain/awv202</idno><idno type="wicri:Area/PubMed/Corpus">000420</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000420</idno><idno type="wicri:Area/PubMed/Curation">000420</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000420</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.</title><author><name sortKey="Locascio, Joseph J" sort="Locascio, Joseph J" uniqKey="Locascio J" first="Joseph J" last="Locascio">Joseph J. Locascio</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Eberly, Shirley" sort="Eberly, Shirley" uniqKey="Eberly S" first="Shirley" last="Eberly">Shirley Eberly</name><affiliation wicri:level="1"><nlm:affiliation>3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642</wicri:regionArea></affiliation></author><author><name sortKey="Liao, Zhixiang" sort="Liao, Zhixiang" uniqKey="Liao Z" first="Zhixiang" last="Liao">Zhixiang Liao</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Ganqiang" sort="Liu, Ganqiang" uniqKey="Liu G" first="Ganqiang" last="Liu">Ganqiang Liu</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Hoesing, Ashley N" sort="Hoesing, Ashley N" uniqKey="Hoesing A" first="Ashley N" last="Hoesing">Ashley N. Hoesing</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Duong, Karen" sort="Duong, Karen" uniqKey="Duong K" first="Karen" last="Duong">Karen Duong</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Trisini Lipsanopoulos, Ana" sort="Trisini Lipsanopoulos, Ana" uniqKey="Trisini Lipsanopoulos A" first="Ana" last="Trisini-Lipsanopoulos">Ana Trisini-Lipsanopoulos</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Dhima, Kaltra" sort="Dhima, Kaltra" uniqKey="Dhima K" first="Kaltra" last="Dhima">Kaltra Dhima</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Hung, Albert Y" sort="Hung, Albert Y" uniqKey="Hung A" first="Albert Y" last="Hung">Albert Y. Hung</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Flaherty, Alice W" sort="Flaherty, Alice W" uniqKey="Flaherty A" first="Alice W" last="Flaherty">Alice W. Flaherty</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 6 Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 6 Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Schwarzschild, Michael A" sort="Schwarzschild, Michael A" uniqKey="Schwarzschild M" first="Michael A" last="Schwarzschild">Michael A. Schwarzschild</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Hayes, Michael T" sort="Hayes, Michael T" uniqKey="Hayes M" first="Michael T" last="Hayes">Michael T. Hayes</name><affiliation wicri:level="1"><nlm:affiliation>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Wills, Anne Marie" sort="Wills, Anne Marie" uniqKey="Wills A" first="Anne-Marie" last="Wills">Anne-Marie Wills</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Shivraj Sohur, U" sort="Shivraj Sohur, U" uniqKey="Shivraj Sohur U" first="U" last="Shivraj Sohur">U. Shivraj Sohur</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Mejia, Nicte I" sort="Mejia, Nicte I" uniqKey="Mejia N" first="Nicte I" last="Mejia">Nicte I. Mejia</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Selkoe, Dennis J" sort="Selkoe, Dennis J" uniqKey="Selkoe D" first="Dennis J" last="Selkoe">Dennis J. Selkoe</name><affiliation wicri:level="1"><nlm:affiliation>4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Oakes, David" sort="Oakes, David" uniqKey="Oakes D" first="David" last="Oakes">David Oakes</name><affiliation wicri:level="1"><nlm:affiliation>3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642</wicri:regionArea></affiliation></author><author><name sortKey="Shoulson, Ira" sort="Shoulson, Ira" uniqKey="Shoulson I" first="Ira" last="Shoulson">Ira Shoulson</name><affiliation wicri:level="1"><nlm:affiliation>8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007</wicri:regionArea></affiliation></author><author><name sortKey="Dong, Xianjun" sort="Dong, Xianjun" uniqKey="Dong X" first="Xianjun" last="Dong">Xianjun Dong</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Marek, Ken" sort="Marek, Ken" uniqKey="Marek K" first="Ken" last="Marek">Ken Marek</name><affiliation wicri:level="1"><nlm:affiliation>8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007</wicri:regionArea></affiliation></author><author><name sortKey="Zheng, Bin" sort="Zheng, Bin" uniqKey="Zheng B" first="Bin" last="Zheng">Bin Zheng</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Ivinson, Adrian" sort="Ivinson, Adrian" uniqKey="Ivinson A" first="Adrian" last="Ivinson">Adrian Ivinson</name><affiliation wicri:level="1"><nlm:affiliation>4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Hyman, Bradley T" sort="Hyman, Bradley T" uniqKey="Hyman B" first="Bradley T" last="Hyman">Bradley T. Hyman</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Growdon, John H" sort="Growdon, John H" uniqKey="Growdon J" first="John H" last="Growdon">John H. Growdon</name><affiliation wicri:level="1"><nlm:affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114</wicri:regionArea></affiliation></author><author><name sortKey="Sudarsky, Lewis R" sort="Sudarsky, Lewis R" uniqKey="Sudarsky L" first="Lewis R" last="Sudarsky">Lewis R. Sudarsky</name><affiliation wicri:level="1"><nlm:affiliation>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author><author><name sortKey="Schlossmacher, Michael G" sort="Schlossmacher, Michael G" uniqKey="Schlossmacher M" first="Michael G" last="Schlossmacher">Michael G. Schlossmacher</name><affiliation wicri:level="1"><nlm:affiliation>9 Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>9 Institute for Neurodegenerative Disorders, New Haven, CT 06510</wicri:regionArea></affiliation></author><author><name sortKey="Ravina, Bernard" sort="Ravina, Bernard" uniqKey="Ravina B" first="Bernard" last="Ravina">Bernard Ravina</name><affiliation wicri:level="1"><nlm:affiliation>10 Program in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1H8M5, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>10 Program in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1H8M5</wicri:regionArea></affiliation></author><author><name sortKey="Scherzer, Clemens R" sort="Scherzer, Clemens R" uniqKey="Scherzer C" first="Clemens R" last="Scherzer">Clemens R. Scherzer</name><affiliation wicri:level="1"><nlm:affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA cscherzer@rics.bwh.harvard.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115</wicri:regionArea></affiliation></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="eISSN">1460-2156</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Cognition Disorders (etiology)</term><term>Cognition Disorders (genetics)</term><term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term><term>Female</term><term>Gene Expression Regulation</term><term>Genetic Testing</term><term>Humans</term><term>Male</term><term>Microarray Analysis</term><term>Middle Aged</term><term>Neuroimaging</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (diagnostic imaging)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (pathology)</term><term>RNA, Messenger (metabolism)</term><term>Radionuclide Imaging</term><term>Severity of Illness Index</term><term>Tropanes</term><term>alpha-Synuclein (blood)</term><term>alpha-Synuclein (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine Plasma Membrane Transport Proteins</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cognition Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cognition Disorders</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Gene Expression Regulation</term><term>Genetic Testing</term><term>Humans</term><term>Male</term><term>Microarray Analysis</term><term>Middle Aged</term><term>Neuroimaging</term><term>Radionuclide Imaging</term><term>Severity of Illness Index</term><term>Tropanes</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26220939</PMID><DateCreated><Year>2015</Year><Month>08</Month><Day>25</Day></DateCreated><DateCompleted><Year>2015</Year><Month>11</Month><Day>16</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2156</ISSN><JournalIssue CitedMedium="Internet"><Volume>138</Volume><Issue>Pt 9</Issue><PubDate><Year>2015</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Brain : a journal of neurology</Title><ISOAbbreviation>Brain</ISOAbbreviation></Journal><ArticleTitle>Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>2659-71</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/brain/awv202</ELocationID><Abstract><AbstractText>There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P < 0.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.</AbstractText><CopyrightInformation>© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Locascio</LastName><ForeName>Joseph J</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eberly</LastName><ForeName>Shirley</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liao</LastName><ForeName>Zhixiang</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Ganqiang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoesing</LastName><ForeName>Ashley N</ForeName><Initials>AN</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duong</LastName><ForeName>Karen</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trisini-Lipsanopoulos</LastName><ForeName>Ana</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dhima</LastName><ForeName>Kaltra</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hung</LastName><ForeName>Albert Y</ForeName><Initials>AY</Initials><AffiliationInfo><Affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flaherty</LastName><ForeName>Alice W</ForeName><Initials>AW</Initials><AffiliationInfo><Affiliation>2 Department of 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ValidYN="Y"><LastName>Oakes</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shoulson</LastName><ForeName>Ira</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dong</LastName><ForeName>Xianjun</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marek</LastName><ForeName>Ken</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Bin</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ivinson</LastName><ForeName>Adrian</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hyman</LastName><ForeName>Bradley T</ForeName><Initials>BT</Initials><AffiliationInfo><Affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Growdon</LastName><ForeName>John H</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sudarsky</LastName><ForeName>Lewis R</ForeName><Initials>LR</Initials><AffiliationInfo><Affiliation>7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schlossmacher</LastName><ForeName>Michael G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>9 Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ravina</LastName><ForeName>Bernard</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>10 Program in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1H8M5, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scherzer</LastName><ForeName>Clemens R</ForeName><Initials>CR</Initials><AffiliationInfo><Affiliation>1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA cscherzer@rics.bwh.harvard.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>U01 NS082080</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS064155</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 AG005134</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U01 NS082157</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>NS050095</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS083845</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>07</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Brain</MedlineTA><NlmUniqueID>0372537</NlmUniqueID><ISSNLinking>0006-8950</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050483">Dopamine Plasma Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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