ParkinsonCanadaV1, Pmc, Corpus, bibRecord, 000029

Glucocerebrosidase activity in Parkinson’s disease with and without GBA mutations

Identifieur interne : 000029 ( Pmc/Corpus ); précédent : 000028; suivant : 000030

Glucocerebrosidase activity in Parkinson’s disease with and without GBA mutations

Auteurs : Roy N. Alcalay ; Oren A. Levy ; Cheryl C. Waters ; Stanley Fahn ; Blair Ford ; Sheng-Han Kuo ; Pietro Mazzoni ; Michael W. Pauciulo ; William C. Nichols ; Ziv Gan-Or ; Guy A. Rouleau ; Wendy K. Chung ; Pavlina Wolf ; Petra Oliva ; Joan Keutzer ; Karen Marder ; Xiaokui Zhang

Source :

Brain [ 0006-8950 ] ; 2015.

RBID : PMC:4564023

Abstract

Glucocerebrosidase (GBA) mutations are common risk factors for Parkinson’s disease. Alcalay et al. measure glucocerebrosidase enzymatic activity in dried blood spots from patients with Parkinson’s disease with and without GBA mutations, and controls. Low glucocerebrosidase enzymatic activity is strongly associated with GBA mutations, and modestly associated with idiopathic Parkinson’s disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564023

DOI: 10.1093/brain/awv179
PubMed: 26117366
PubMed Central: 4564023

Links to Exploration step

PMC:4564023

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Glucocerebrosidase activity in Parkinson’s disease with and without <italic>GBA</italic>
 mutations</title>
<author><name sortKey="Alcalay, Roy N" sort="Alcalay, Roy N" uniqKey="Alcalay R" first="Roy N." last="Alcalay">Roy N. Alcalay</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Levy, Oren A" sort="Levy, Oren A" uniqKey="Levy O" first="Oren A." last="Levy">Oren A. Levy</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Waters, Cheryl C" sort="Waters, Cheryl C" uniqKey="Waters C" first="Cheryl C." last="Waters">Cheryl C. Waters</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fahn, Stanley" sort="Fahn, Stanley" uniqKey="Fahn S" first="Stanley" last="Fahn">Stanley Fahn</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ford, Blair" sort="Ford, Blair" uniqKey="Ford B" first="Blair" last="Ford">Blair Ford</name>
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</affiliation>
</author>
<author><name sortKey="Kuo, Sheng Han" sort="Kuo, Sheng Han" uniqKey="Kuo S" first="Sheng-Han" last="Kuo">Sheng-Han Kuo</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mazzoni, Pietro" sort="Mazzoni, Pietro" uniqKey="Mazzoni P" first="Pietro" last="Mazzoni">Pietro Mazzoni</name>
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</affiliation>
</author>
<author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name>
<affiliation><nlm:aff id="awv179-AFF3">3 Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics; University of Cincinnati College of Medicine, Cincinnati, OH, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name>
<affiliation><nlm:aff id="awv179-AFF3">3 Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics; University of Cincinnati College of Medicine, Cincinnati, OH, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gan Or, Ziv" sort="Gan Or, Ziv" uniqKey="Gan Or Z" first="Ziv" last="Gan-Or">Ziv Gan-Or</name>
<affiliation><nlm:aff id="awv179-AFF4">4 Montréal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name>
<affiliation><nlm:aff id="awv179-AFF4">4 Montréal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chung, Wendy K" sort="Chung, Wendy K" uniqKey="Chung W" first="Wendy K." last="Chung">Wendy K. Chung</name>
<affiliation><nlm:aff id="awv179-AFF5">5 Department of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wolf, Pavlina" sort="Wolf, Pavlina" uniqKey="Wolf P" first="Pavlina" last="Wolf">Pavlina Wolf</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oliva, Petra" sort="Oliva, Petra" uniqKey="Oliva P" first="Petra" last="Oliva">Petra Oliva</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Keutzer, Joan" sort="Keutzer, Joan" uniqKey="Keutzer J" first="Joan" last="Keutzer">Joan Keutzer</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF7">7 Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Xiaokui" sort="Zhang, Xiaokui" uniqKey="Zhang X" first="Xiaokui" last="Zhang">Xiaokui Zhang</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Glucocerebrosidase activity in Parkinson’s disease with and without <italic>GBA</italic>
 mutations</title>
<author><name sortKey="Alcalay, Roy N" sort="Alcalay, Roy N" uniqKey="Alcalay R" first="Roy N." last="Alcalay">Roy N. Alcalay</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Levy, Oren A" sort="Levy, Oren A" uniqKey="Levy O" first="Oren A." last="Levy">Oren A. Levy</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Waters, Cheryl C" sort="Waters, Cheryl C" uniqKey="Waters C" first="Cheryl C." last="Waters">Cheryl C. Waters</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Fahn, Stanley" sort="Fahn, Stanley" uniqKey="Fahn S" first="Stanley" last="Fahn">Stanley Fahn</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ford, Blair" sort="Ford, Blair" uniqKey="Ford B" first="Blair" last="Ford">Blair Ford</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuo, Sheng Han" sort="Kuo, Sheng Han" uniqKey="Kuo S" first="Sheng-Han" last="Kuo">Sheng-Han Kuo</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mazzoni, Pietro" sort="Mazzoni, Pietro" uniqKey="Mazzoni P" first="Pietro" last="Mazzoni">Pietro Mazzoni</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Pauciulo, Michael W" sort="Pauciulo, Michael W" uniqKey="Pauciulo M" first="Michael W." last="Pauciulo">Michael W. Pauciulo</name>
<affiliation><nlm:aff id="awv179-AFF3">3 Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics; University of Cincinnati College of Medicine, Cincinnati, OH, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nichols, William C" sort="Nichols, William C" uniqKey="Nichols W" first="William C." last="Nichols">William C. Nichols</name>
<affiliation><nlm:aff id="awv179-AFF3">3 Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics; University of Cincinnati College of Medicine, Cincinnati, OH, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gan Or, Ziv" sort="Gan Or, Ziv" uniqKey="Gan Or Z" first="Ziv" last="Gan-Or">Ziv Gan-Or</name>
<affiliation><nlm:aff id="awv179-AFF4">4 Montréal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rouleau, Guy A" sort="Rouleau, Guy A" uniqKey="Rouleau G" first="Guy A." last="Rouleau">Guy A. Rouleau</name>
<affiliation><nlm:aff id="awv179-AFF4">4 Montréal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Chung, Wendy K" sort="Chung, Wendy K" uniqKey="Chung W" first="Wendy K." last="Chung">Wendy K. Chung</name>
<affiliation><nlm:aff id="awv179-AFF5">5 Department of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wolf, Pavlina" sort="Wolf, Pavlina" uniqKey="Wolf P" first="Pavlina" last="Wolf">Pavlina Wolf</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Oliva, Petra" sort="Oliva, Petra" uniqKey="Oliva P" first="Petra" last="Oliva">Petra Oliva</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Keutzer, Joan" sort="Keutzer, Joan" uniqKey="Keutzer J" first="Joan" last="Keutzer">Joan Keutzer</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Marder, Karen" sort="Marder, Karen" uniqKey="Marder K" first="Karen" last="Marder">Karen Marder</name>
<affiliation><nlm:aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="awv179-AFF7">7 Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zhang, Xiaokui" sort="Zhang, Xiaokui" uniqKey="Zhang X" first="Xiaokui" last="Zhang">Xiaokui Zhang</name>
<affiliation><nlm:aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Brain</title>
<idno type="ISSN">0006-8950</idno>
<idno type="eISSN">1460-2156</idno>
<imprint><date when="2015">2015</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>Glucocerebrosidase (<italic>GBA</italic>
) mutations are common risk factors for Parkinson’s disease. Alcalay <italic>et al.</italic>
 measure glucocerebrosidase enzymatic activity in dried blood spots from patients with Parkinson’s disease with and without <italic>GBA</italic>
 mutations, and controls. Low glucocerebrosidase enzymatic activity is strongly associated with <italic>GBA</italic>
 mutations, and modestly associated with idiopathic Parkinson’s disease.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <front><journal-meta><journal-id journal-id-type="nlm-ta">Brain</journal-id>
<journal-id journal-id-type="iso-abbrev">Brain</journal-id>
<journal-id journal-id-type="publisher-id">brainj</journal-id>
<journal-id journal-id-type="hwp">brain</journal-id>
<journal-title-group><journal-title>Brain</journal-title>
</journal-title-group>
<issn pub-type="ppub">0006-8950</issn>
<issn pub-type="epub">1460-2156</issn>
<publisher><publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26117366</article-id>
<article-id pub-id-type="pmc">4564023</article-id>
<article-id pub-id-type="doi">10.1093/brain/awv179</article-id>
<article-id pub-id-type="publisher-id">awv179</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject>
</subj-group>
<subj-group subj-group-type="hwp-journal-coll"><subject>1040</subject>
</subj-group>
</article-categories>
<title-group><article-title>Glucocerebrosidase activity in Parkinson’s disease with and without <italic>GBA</italic>
 mutations</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Alcalay</surname>
<given-names>Roy N.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="awv179-AFF2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Levy</surname>
<given-names>Oren A.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="awv179-AFF2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Waters</surname>
<given-names>Cheryl C.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fahn</surname>
<given-names>Stanley</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ford</surname>
<given-names>Blair</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuo</surname>
<given-names>Sheng-Han</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mazzoni</surname>
<given-names>Pietro</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pauciulo</surname>
<given-names>Michael W.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nichols</surname>
<given-names>William C.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF3"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gan-Or</surname>
<given-names>Ziv</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rouleau</surname>
<given-names>Guy A.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF4"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chung</surname>
<given-names>Wendy K.</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF5"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wolf</surname>
<given-names>Pavlina</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Oliva</surname>
<given-names>Petra</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Keutzer</surname>
<given-names>Joan</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF6"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Marder</surname>
<given-names>Karen</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF1"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="awv179-AFF2"><sup>2</sup>
</xref>
<xref ref-type="aff" rid="awv179-AFF7"><sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Xiaokui</given-names>
</name>
<xref ref-type="aff" rid="awv179-AFF6"><sup>6</sup>
</xref>
</contrib>
<aff id="awv179-AFF1">1 Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</aff>
<aff id="awv179-AFF2">2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</aff>
<aff id="awv179-AFF3">3 Division of Human Genetics, Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics; University of Cincinnati College of Medicine, Cincinnati, OH, USA</aff>
<aff id="awv179-AFF4">4 Montréal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada</aff>
<aff id="awv179-AFF5">5 Department of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA</aff>
<aff id="awv179-AFF6">6 Global BioTherapeutics, Genzyme, a Sanofi company, Framingham, MA, USA</aff>
<aff id="awv179-AFF7">7 Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA</aff>
</contrib-group>
<author-notes><corresp id="awv179-COR1">Correspondence to: Roy N. Alcalay, 710 West 168th street, New York City, New York USA E-mail: <email>rna2104@columbia.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>9</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>27</day>
<month>6</month>
<year>2015</year>
</pub-date>
<volume>138</volume>
<issue>9</issue>
<fpage>2648</fpage>
<lpage>2658</lpage>
<history><date date-type="received"><day>28</day>
<month>1</month>
<year>2015</year>
</date>
<date date-type="rev-recd"><day>01</day>
<month>4</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>27</day>
<month>4</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© 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</copyright-statement>
<copyright-year>2015</copyright-year>
</permissions>
<abstract abstract-type="precis"><p>Glucocerebrosidase (<italic>GBA</italic>
) mutations are common risk factors for Parkinson’s disease. Alcalay <italic>et al.</italic>
 measure glucocerebrosidase enzymatic activity in dried blood spots from patients with Parkinson’s disease with and without <italic>GBA</italic>
 mutations, and controls. Low glucocerebrosidase enzymatic activity is strongly associated with <italic>GBA</italic>
 mutations, and modestly associated with idiopathic Parkinson’s disease.</p>
</abstract>
<abstract abstract-type="graphical"><p><fig id="fig1g" fig-type="featured" position="float"><caption><p>Glucocerebrosidase (<italic>GBA</italic>
) mutations are common risk factors for Parkinson’s disease. Alcalay <italic>et al.</italic>
 measure glucocerebrosidase enzymatic activity in dried blood spots from patients with Parkinson’s disease with and without <italic>GBA</italic>
 mutations, and controls. Low glucocerebrosidase enzymatic activity is strongly associated with <italic>GBA</italic>
 mutations, and modestly associated with idiopathic Parkinson’s disease.</p>
</caption>
<graphic xlink:href="awv179fig1g"></graphic>
</fig>
</p>
</abstract>
<abstract><p>Glucocerebrosidase (<italic>GBA</italic>
) mutations have been associated with Parkinson’s disease in numerous studies. However, it is unknown whether the increased risk of Parkinson’s disease in <italic>GBA</italic>
 carriers is due to a loss of glucocerebrosidase enzymatic activity. We measured glucocerebrosidase enzymatic activity in dried blood spots in patients with Parkinson's disease (<italic>n = </italic>
517) and controls (<italic>n = </italic>
252) with and without <italic>GBA</italic>
 mutations. Participants were recruited from Columbia University, New York, and fully sequenced for <italic>GBA</italic>
 mutations and genotyped for the <italic>LRRK2</italic>
 G2019S mutation, the most common autosomal dominant mutation in the Ashkenazi Jewish population. Glucocerebrosidase enzymatic activity in dried blood spots was measured by a mass spectrometry-based assay and compared among participants categorized by <italic>GBA</italic>
 mutation status and Parkinson’s disease diagnosis. Parkinson’s disease patients were more likely than controls to carry the <italic>LRRK2</italic>
 G2019S mutation (<italic>n = </italic>
39, 7.5% versus <italic>n = </italic>
2, 0.8%, <italic>P < </italic>
0.001) and <italic>GBA</italic>
 mutations or variants (seven homozygotes and compound heterozygotes and 81 heterozygotes, 17.0% versus 17 heterozygotes, 6.7%, <italic>P < </italic>
0.001). <italic>GBA</italic>
 homozygotes/compound heterozygotes had lower enzymatic activity than <italic>GBA </italic>
heterozygotes (0.85 µmol/l/h versus 7.88 µmol/l/h, <italic>P < </italic>
0.001), and <italic>GBA</italic>
 heterozygotes had lower enzymatic activity than <italic>GBA</italic>
 and <italic>LRRK2 </italic>
non-carriers (7.88 µmol/l/h versus 11.93 µmol/l/h, <italic>P < </italic>
0.001). Glucocerebrosidase activity was reduced in heterozygotes compared to non-carriers when each mutation was compared independently (N370S, <italic>P < </italic>
0.001; L444P, <italic>P < </italic>
0.001; 84GG, <italic>P = </italic>
0.003; R496H, <italic>P = </italic>
0.018) and also reduced in <italic>GBA</italic>
 variants associated with Parkinson’s risk but not with Gaucher disease (E326K, <italic>P = </italic>
0.009; T369M, <italic>P < </italic>
0.001). When all patients with Parkinson’s disease were considered, they had lower mean glucocerebrosidase enzymatic activity than controls (11.14 µmol/l/h versus 11.85 µmol/l/h, <italic>P = </italic>
0.011). Difference compared to controls persisted in patients with idiopathic Parkinson’s disease (after exclusion of all <italic>GBA</italic>
 and <italic>LRRK2</italic>
 carriers; 11.53 µmol/l/h, versus 12.11 µmol/l/h, <italic>P = </italic>
0.036) and after adjustment for age and gender (<italic>P = </italic>
0.012). Interestingly, <italic>LRRK2</italic>
 G2019S carriers (<italic>n = </italic>
36), most of whom had Parkinson’s disease, had higher enzymatic activity than non-carriers (13.69 µmol/l/h versus 11.93 µmol/l/h, <italic>P = </italic>
0.002). In patients with idiopathic Parkinson’s, higher glucocerebrosidase enzymatic activity was associated with longer disease duration (<italic>P = </italic>
0.002) in adjusted models, suggesting a milder disease course. We conclude that lower glucocerebrosidase enzymatic activity is strongly associated with <italic>GBA</italic>
 mutations, and modestly with idiopathic Parkinson’s disease. The association of lower glucocerebrosidase activity in both <italic>GBA</italic>
 mutation carriers and Parkinson’s patients without <italic>GBA</italic>
 mutations suggests that loss of glucocerebrosidase function contributes to the pathogenesis of Parkinson’s disease. High glucocerebrosidase enzymatic activity in <italic>LRRK2</italic>
 G2019S carriers may reflect a distinct pathogenic mechanism. Taken together, these data suggest that glucocerebrosidase enzymatic activity could be a modifiable therapeutic target.</p>
</abstract>
<kwd-group kwd-group-type="keywords"><kwd>Parkinson’s disease</kwd>
<kwd>glucocerebrosidase</kwd>
<kwd>lysosome</kwd>
<kwd>genetics</kwd>
<kwd>LRRK2</kwd>
</kwd-group>
<counts><page-count count="11"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>

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Glucocerebrosidase activity in Parkinson’s disease with and without GBA mutations

Glucocerebrosidase activity in Parkinson’s disease with and without GBA mutations

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