Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and Progression
Identifieur interne : 000215 ( Pmc/Curation ); précédent : 000214; suivant : 000216Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and Progression
Auteurs : Min Shi [États-Unis] ; Joshua Bradner [États-Unis] ; Aneeka Hancock [États-Unis] ; Kathryn Chung [États-Unis] ; Joseph Quinn [États-Unis] ; Elaine Peskind [États-Unis] ; Douglas Galasko [États-Unis] ; Joseph Jankovic [États-Unis] ; Cyrus Zabetian [États-Unis] ; Hojoong Kim [États-Unis] ; James Leverenz [États-Unis] ; Thomas Montine [États-Unis] ; Carmen Ginghina [États-Unis] ; Un Kang [États-Unis] ; Kevin Cain [États-Unis] ; Yu Wang [États-Unis, République populaire de Chine] ; Jan Aasly [Norvège] ; David Goldstein [États-Unis] ; Jing Zhang [États-Unis]Source :
- Annals of neurology [ 0364-5134 ] ; 2011.
Abstract
There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for PD diagnosis, but not for PD severity.
Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (Aβ1-42), Flt3 ligand and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these five markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and α-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally.
The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/Aβ1-42 that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples.
We have demonstrated that this panel of seven CSF proteins could aid in PD diagnosis, differential diagnosis, and correlation with disease severity and progression.
Url:
DOI: 10.1002/ana.22311
PubMed: 21400565
PubMed Central: 3117674
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<country xml:lang="fr">République populaire de Chine</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and Progression</title>
<author><name sortKey="Shi, Min" sort="Shi, Min" uniqKey="Shi M" first="Min" last="Shi">Min Shi</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Bradner, Joshua" sort="Bradner, Joshua" uniqKey="Bradner J" first="Joshua" last="Bradner">Joshua Bradner</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
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<author><name sortKey="Hancock, Aneeka M" sort="Hancock, Aneeka M" uniqKey="Hancock A" first="Aneeka" last="Hancock">Aneeka Hancock</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
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<author><name sortKey="Chung, Kathryn A" sort="Chung, Kathryn A" uniqKey="Chung K" first="Kathryn" last="Chung">Kathryn Chung</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Department of Neurology, Oregon Health and Science University, Portland, OR, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Oregon Health and Science University, Portland, OR</wicri:regionArea>
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<author><name sortKey="Quinn, Joseph F" sort="Quinn, Joseph F" uniqKey="Quinn J" first="Joseph" last="Quinn">Joseph Quinn</name>
<affiliation wicri:level="1"><nlm:aff id="A2">Department of Neurology, Oregon Health and Science University, Portland, OR, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Oregon Health and Science University, Portland, OR</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Peskind, Elaine R" sort="Peskind, Elaine R" uniqKey="Peskind E" first="Elaine" last="Peskind">Elaine Peskind</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A4">Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA</wicri:regionArea>
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<author><name sortKey="Galasko, Douglas" sort="Galasko, Douglas" uniqKey="Galasko D" first="Douglas" last="Galasko">Douglas Galasko</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Department of Neurosciences, University of California at San Diego, San Diego, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurosciences, University of California at San Diego, San Diego, CA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX</wicri:regionArea>
</affiliation>
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<author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus" last="Zabetian">Cyrus Zabetian</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A8">Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Kim, Hojoong M" sort="Kim, Hojoong M" uniqKey="Kim H" first="Hojoong" last="Kim">Hojoong Kim</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="A8">Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
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<author><name sortKey="Leverenz, James B" sort="Leverenz, James B" uniqKey="Leverenz J" first="James" last="Leverenz">James Leverenz</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Montine, Thomas J" sort="Montine, Thomas J" uniqKey="Montine T" first="Thomas" last="Montine">Thomas Montine</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
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<author><name sortKey="Ginghina, Carmen" sort="Ginghina, Carmen" uniqKey="Ginghina C" first="Carmen" last="Ginghina">Carmen Ginghina</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kang, Un Jung" sort="Kang, Un Jung" uniqKey="Kang U" first="Un" last="Kang">Un Kang</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Department of Neurology, University of Chicago, Chicago, IL, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Chicago, Chicago, IL</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cain, Kevin C" sort="Cain, Kevin C" uniqKey="Cain K" first="Kevin" last="Cain">Kevin Cain</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Biostatistics, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A11">Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan</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:aff id="A12">Department of Neurology, St. Olavs Hospital, Trondheim, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Department of Neurology, St. Olavs Hospital, Trondheim</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goldstein, David S" sort="Goldstein, David S" uniqKey="Goldstein D" first="David" last="Goldstein">David Goldstein</name>
<affiliation wicri:level="1"><nlm:aff id="A13">Clinical Neurocardiology Section, CNP, DIR, NINDS, NIH, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Clinical Neurocardiology Section, CNP, DIR, NINDS, NIH, Bethesda, MD</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:aff id="A1">Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Washington School of Medicine, Seattle, WA</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Annals of neurology</title>
<idno type="ISSN">0364-5134</idno>
<idno type="e-ISSN">1531-8249</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title>
<p id="P1">There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for PD diagnosis, but not for PD severity.</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods</title>
<p id="P2">Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (Aβ<sub>1-42</sub>
), Flt3 ligand and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these five markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and α-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally.</p>
</sec>
<sec id="S3"><title>Findings</title>
<p id="P3">The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/Aβ<sub>1-42</sub>
that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P4">We have demonstrated that this panel of seven CSF proteins could aid in PD diagnosis, differential diagnosis, and correlation with disease severity and progression.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="en"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">7707449</journal-id>
<journal-id journal-id-type="pubmed-jr-id">656</journal-id>
<journal-id journal-id-type="nlm-ta">Ann Neurol</journal-id>
<journal-title-group><journal-title>Annals of neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0364-5134</issn>
<issn pub-type="epub">1531-8249</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21400565</article-id>
<article-id pub-id-type="pmc">3117674</article-id>
<article-id pub-id-type="doi">10.1002/ana.22311</article-id>
<article-id pub-id-type="manuscript">NIHMS294720</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and Progression</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Shi</surname>
<given-names>Min</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bradner</surname>
<given-names>Joshua</given-names>
</name>
<degrees>MS</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hancock</surname>
<given-names>Aneeka M.</given-names>
</name>
<degrees>BS</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chung</surname>
<given-names>Kathryn A.</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Quinn</surname>
<given-names>Joseph F.</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A2" ref-type="aff">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peskind</surname>
<given-names>Elaine R.</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A3" ref-type="aff">3</xref>
<xref rid="A4" ref-type="aff">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Galasko</surname>
<given-names>Douglas</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A5" ref-type="aff">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jankovic</surname>
<given-names>Joseph</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A6" ref-type="aff">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zabetian</surname>
<given-names>Cyrus P.</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A7" ref-type="aff">7</xref>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kim</surname>
<given-names>Hojoong M.</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A7" ref-type="aff">7</xref>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Leverenz</surname>
<given-names>James B.</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A3" ref-type="aff">3</xref>
<xref rid="A4" ref-type="aff">4</xref>
<xref rid="A8" ref-type="aff">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Montine</surname>
<given-names>Thomas J.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ginghina</surname>
<given-names>Carmen</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kang</surname>
<given-names>Un Jung</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A9" ref-type="aff">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cain</surname>
<given-names>Kevin C.</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="A10" ref-type="aff">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Yu</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="A11" ref-type="aff">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Aasly</surname>
<given-names>Jan</given-names>
</name>
<degrees>MD</degrees>
<xref rid="A12" ref-type="aff">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Goldstein</surname>
<given-names>David S.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref rid="A13" ref-type="aff">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zhang</surname>
<given-names>Jing</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref rid="A1" ref-type="aff">1</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA</aff>
<aff id="A2"><label>2</label>
Department of Neurology, Oregon Health and Science University, Portland, OR, USA</aff>
<aff id="A3"><label>3</label>
Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA</aff>
<aff id="A4"><label>4</label>
Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA</aff>
<aff id="A5"><label>5</label>
Department of Neurosciences, University of California at San Diego, San Diego, CA, USA</aff>
<aff id="A6"><label>6</label>
Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX, USA</aff>
<aff id="A7"><label>7</label>
Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA</aff>
<aff id="A8"><label>8</label>
Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA</aff>
<aff id="A9"><label>9</label>
Department of Neurology, University of Chicago, Chicago, IL, USA</aff>
<aff id="A10"><label>10</label>
Department of Biostatistics, University of Washington School of Medicine, Seattle, WA, USA</aff>
<aff id="A11"><label>11</label>
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China</aff>
<aff id="A12"><label>12</label>
Department of Neurology, St. Olavs Hospital, Trondheim, Norway</aff>
<aff id="A13"><label>13</label>
Clinical Neurocardiology Section, CNP, DIR, NINDS, NIH, Bethesda, MD, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Address correspondence to: Jing Zhang, Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9<sup>th</sup>
Ave, Seattle, WA 98104, USA. Phone: 1-206-897-5245, Fax: 1-206-897-5452, <email>zhangj@uw.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>20</day>
<month>5</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>11</day>
<month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>11</day>
<month>3</month>
<year>2012</year>
</pub-date>
<volume>69</volume>
<issue>3</issue>
<fpage>570</fpage>
<lpage>580</lpage>
<abstract><sec id="S1"><title>Background</title>
<p id="P1">There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or α-synuclein in the cerebrospinal fluid (CSF) is a potential index for PD diagnosis, but not for PD severity.</p>
</sec>
<sec sec-type="methods" id="S2"><title>Methods</title>
<p id="P2">Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (Aβ<sub>1-42</sub>
), Flt3 ligand and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these five markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and α-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally.</p>
</sec>
<sec id="S3"><title>Findings</title>
<p id="P3">The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/Aβ<sub>1-42</sub>
that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples.</p>
</sec>
<sec id="S4"><title>Interpretation</title>
<p id="P4">We have demonstrated that this panel of seven CSF proteins could aid in PD diagnosis, differential diagnosis, and correlation with disease severity and progression.</p>
</sec>
</abstract>
<funding-group><award-group><funding-source country="United States">National Center for Research Resources : NCRR</funding-source>
<award-id>UL1 RR025014-04 || RR</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R21 NS060252-02 || NS</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS065070-03 || NS</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS065070-02 || NS</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS057567-04 || NS</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>R01 AG033398-04 || AG</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>R01 AG025327-05 || AG</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>P50 NS062684-02 || NS</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>P50 AG005136-19 || AG</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute of Environmental Health Sciences : NIEHS</funding-source>
<award-id>P42 ES004696-20 || ES</award-id>
</award-group>
<award-group><funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>P30 AG008017-14 || AG</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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