DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease.
Identifieur interne : 000098 ( PubMed/Corpus ); précédent : 000097; suivant : 000099DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease.
Auteurs : Zhen Hong ; Min Shi ; Kathryn. Chung ; Joseph. Quinn ; Elaine. Peskind ; Douglas Galasko ; Joseph Jankovic ; Cyrus. Zabetian ; James. Leverenz ; Geoffrey Baird ; Thomas. Montine ; Aneeka. Hancock ; Hyejin Hwang ; Catherine Pan ; Joshua Bradner ; Un. Kang ; Poul. Jensen ; Jing ZhangSource :
- Brain : a journal of neurology ; 2010.
English descriptors
- KwdEn :
- Adult, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease (cerebrospinal fluid), Biomarkers (cerebrospinal fluid), Blood (metabolism), Cerebrospinal Fluid (metabolism), Female, Humans, Intracellular Signaling Peptides and Proteins (cerebrospinal fluid), Male, Middle Aged, Oncogene Proteins (cerebrospinal fluid), Parkinson Disease (cerebrospinal fluid), Sensitivity and Specificity, Severity of Illness Index, Sex Factors, Young Adult, alpha-Synuclein (cerebrospinal fluid).
- MESH :
- chemical , cerebrospinal fluid : Biomarkers, Intracellular Signaling Peptides and Proteins, Oncogene Proteins, alpha-Synuclein.
- cerebrospinal fluid : Alzheimer Disease, Parkinson Disease.
- metabolism : Blood, Cerebrospinal Fluid.
- Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, Severity of Illness Index, Sex Factors, Young Adult.
Abstract
Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and alpha-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy individuals and 50 patients with Alzheimer's disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in Parkinson's patients versus controls or Alzheimer's patients when blood contamination was controlled for. In the population aged > or = 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein, respectively, the sensitivity and specificity for patients with Parkinson's disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or alpha-synuclein and the severity of Parkinson's disease. Taken together, this represents the largest scale study for DJ-1 or alpha-synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and alpha-synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson's disease, if variables such as blood contamination and age are taken into consideration.
DOI: 10.1093/brain/awq008
PubMed: 20157014
Links to Exploration step
pubmed:20157014Le document en format XML
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Jensen</name></author><author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="doi">10.1093/brain/awq008</idno><idno type="RBID">pubmed:20157014</idno><idno type="pmid">20157014</idno><idno type="wicri:Area/PubMed/Corpus">000098</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease.</title><author><name sortKey="Hong, Zhen" sort="Hong, Zhen" uniqKey="Hong Z" first="Zhen" last="Hong">Zhen Hong</name><affiliation><nlm:affiliation>Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Avenue, Seattle, WA 98104, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Shi, Min" sort="Shi, Min" uniqKey="Shi M" first="Min" last="Shi">Min Shi</name></author><author><name sortKey="Chung, Kathryn A" sort="Chung, Kathryn A" uniqKey="Chung K" first="Kathryn" last="Chung">Kathryn. Chung</name></author><author><name sortKey="Quinn, Joseph F" sort="Quinn, Joseph F" uniqKey="Quinn J" first="Joseph" last="Quinn">Joseph. Quinn</name></author><author><name sortKey="Peskind, Elaine R" sort="Peskind, Elaine R" uniqKey="Peskind E" first="Elaine" last="Peskind">Elaine. Peskind</name></author><author><name sortKey="Galasko, Douglas" sort="Galasko, Douglas" uniqKey="Galasko D" first="Douglas" last="Galasko">Douglas Galasko</name></author><author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus" last="Zabetian">Cyrus. Zabetian</name></author><author><name sortKey="Leverenz, James B" sort="Leverenz, James B" uniqKey="Leverenz J" first="James" last="Leverenz">James. Leverenz</name></author><author><name sortKey="Baird, Geoffrey" sort="Baird, Geoffrey" uniqKey="Baird G" first="Geoffrey" last="Baird">Geoffrey Baird</name></author><author><name sortKey="Montine, Thomas J" sort="Montine, Thomas J" uniqKey="Montine T" first="Thomas" last="Montine">Thomas. Montine</name></author><author><name sortKey="Hancock, Aneeka M" sort="Hancock, Aneeka M" uniqKey="Hancock A" first="Aneeka" last="Hancock">Aneeka. Hancock</name></author><author><name sortKey="Hwang, Hyejin" sort="Hwang, Hyejin" uniqKey="Hwang H" first="Hyejin" last="Hwang">Hyejin Hwang</name></author><author><name sortKey="Pan, Catherine" sort="Pan, Catherine" uniqKey="Pan C" first="Catherine" last="Pan">Catherine Pan</name></author><author><name sortKey="Bradner, Joshua" sort="Bradner, Joshua" uniqKey="Bradner J" first="Joshua" last="Bradner">Joshua Bradner</name></author><author><name sortKey="Kang, Un J" sort="Kang, Un J" uniqKey="Kang U" first="Un" last="Kang">Un. Kang</name></author><author><name sortKey="Jensen, Poul H" sort="Jensen, Poul H" uniqKey="Jensen P" first="Poul" last="Jensen">Poul. Jensen</name></author><author><name sortKey="Zhang, Jing" sort="Zhang, Jing" uniqKey="Zhang J" first="Jing" last="Zhang">Jing Zhang</name></author></analytic><series><title level="j">Brain : a journal of neurology</title><idno type="e-ISSN">1460-2156</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Aged</term><term>Aged, 80 and over</term><term>Alzheimer Disease (cerebrospinal fluid)</term><term>Biomarkers (cerebrospinal fluid)</term><term>Blood (metabolism)</term><term>Cerebrospinal Fluid (metabolism)</term><term>Female</term><term>Humans</term><term>Intracellular Signaling Peptides and Proteins (cerebrospinal fluid)</term><term>Male</term><term>Middle Aged</term><term>Oncogene Proteins (cerebrospinal fluid)</term><term>Parkinson Disease (cerebrospinal fluid)</term><term>Sensitivity and Specificity</term><term>Severity of Illness Index</term><term>Sex Factors</term><term>Young Adult</term><term>alpha-Synuclein (cerebrospinal fluid)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>Biomarkers</term><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Alzheimer Disease</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Blood</term><term>Cerebrospinal Fluid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Age Factors</term><term>Aged</term><term>Aged, 80 and over</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Sensitivity and Specificity</term><term>Severity of Illness Index</term><term>Sex Factors</term><term>Young Adult</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and alpha-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy individuals and 50 patients with Alzheimer's disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in Parkinson's patients versus controls or Alzheimer's patients when blood contamination was controlled for. In the population aged > or = 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein, respectively, the sensitivity and specificity for patients with Parkinson's disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or alpha-synuclein and the severity of Parkinson's disease. Taken together, this represents the largest scale study for DJ-1 or alpha-synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and alpha-synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson's disease, if variables such as blood contamination and age are taken into consideration.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">20157014</PMID><DateCreated><Year>2010</Year><Month>03</Month><Day>22</Day></DateCreated><DateCompleted><Year>2010</Year><Month>04</Month><Day>13</Day></DateCompleted><DateRevised><Year>2015</Year><Month>11</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1460-2156</ISSN><JournalIssue CitedMedium="Internet"><Volume>133</Volume><Issue>Pt 3</Issue><PubDate><Year>2010</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Brain : a journal of neurology</Title><ISOAbbreviation>Brain</ISOAbbreviation></Journal><ArticleTitle>DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>713-26</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/brain/awq008</ELocationID><Abstract><AbstractText>Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson's disease. Both DJ-1 and alpha-synuclein, two proteins critically involved in Parkinson's disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and alpha-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and alpha-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and alpha-synuclein from 117 patients with Parkinson's disease, 132 healthy individuals and 50 patients with Alzheimer's disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and alpha-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and alpha-synuclein levels were decreased in Parkinson's patients versus controls or Alzheimer's patients when blood contamination was controlled for. In the population aged > or = 65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and alpha-synuclein, respectively, the sensitivity and specificity for patients with Parkinson's disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for alpha-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or alpha-synuclein and the severity of Parkinson's disease. Taken together, this represents the largest scale study for DJ-1 or alpha-synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and alpha-synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson's disease, if variables such as blood contamination and age are taken into consideration.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hong</LastName><ForeName>Zhen</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Avenue, Seattle, WA 98104, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shi</LastName><ForeName>Min</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Chung</LastName><ForeName>Kathryn A</ForeName><Initials>KA</Initials></Author><Author ValidYN="Y"><LastName>Quinn</LastName><ForeName>Joseph F</ForeName><Initials>JF</Initials></Author><Author ValidYN="Y"><LastName>Peskind</LastName><ForeName>Elaine R</ForeName><Initials>ER</Initials></Author><Author ValidYN="Y"><LastName>Galasko</LastName><ForeName>Douglas</ForeName><Initials>D</Initials></Author><Author ValidYN="Y"><LastName>Jankovic</LastName><ForeName>Joseph</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Zabetian</LastName><ForeName>Cyrus P</ForeName><Initials>CP</Initials></Author><Author ValidYN="Y"><LastName>Leverenz</LastName><ForeName>James B</ForeName><Initials>JB</Initials></Author><Author ValidYN="Y"><LastName>Baird</LastName><ForeName>Geoffrey</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Montine</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials></Author><Author ValidYN="Y"><LastName>Hancock</LastName><ForeName>Aneeka M</ForeName><Initials>AM</Initials></Author><Author ValidYN="Y"><LastName>Hwang</LastName><ForeName>Hyejin</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Pan</LastName><ForeName>Catherine</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Bradner</LastName><ForeName>Joshua</ForeName><Initials>J</Initials></Author><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Un J</ForeName><Initials>UJ</Initials></Author><Author ValidYN="Y"><LastName>Jensen</LastName><ForeName>Poul H</ForeName><Initials>PH</Initials></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Jing</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>AG025327</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AG033398</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AG05136</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AG08017</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AG08671</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>ES004696</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>NS057567</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>NS060252</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>NS062684</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 AG008017</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P42 ES004696</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 AG005136</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 AG005136-27</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 NS062684</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AG025327</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AG033398</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS053919</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS053919-03</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS057567</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 NS060252</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 RR025014</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 RR025014-01</GrantID><Acronym>RR</Acronym><Agency>NCRR 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><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>02</Month><Day>15</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="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D047908">Intracellular Signaling Peptides and Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015513">Oncogene Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C105131">PARK7 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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2006;22(3):200-8</RefSource><PMID Version="1">16899997</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Neurol. 2007 Apr;204(2):583-8</RefSource><PMID Version="1">17258710</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000367">Age Factors</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000368">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000369">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000544">Alzheimer Disease</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000134">cerebrospinal fluid</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D015415">Biomarkers</DescriptorName><QualifierName MajorTopicYN="N" 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