Detection of disease-associated α-synuclein in the cerebrospinal fluid: a feasibility study.
Identifieur interne : 000513 ( PubMed/Corpus ); précédent : 000512; suivant : 000514Detection of disease-associated α-synuclein in the cerebrospinal fluid: a feasibility study.
Auteurs : Ursula Unterberger ; Ingolf Lachmann ; Till Voigtl Nder ; Walter Pirker ; Anna S. Berghoff ; Katharina Flach ; Uta Wagner ; Aline Geneste ; Armand Perret-Liaudet ; Gabor G. KovacsSource :
- Clinical neuropathology [ 0722-5091 ]
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Alzheimer Disease (cerebrospinal fluid), Alzheimer Disease (diagnosis), Enzyme-Linked Immunosorbent Assay (methods), Enzyme-Linked Immunosorbent Assay (standards), Feasibility Studies, Female, Humans, Immunomagnetic Separation (methods), Immunomagnetic Separation (standards), Lewy Body Disease (cerebrospinal fluid), Lewy Body Disease (diagnosis), Male, Middle Aged, Neurodegenerative Diseases (cerebrospinal fluid), Neurodegenerative Diseases (diagnosis), Parkinson Disease (cerebrospinal fluid), Parkinson Disease (diagnosis), Reproducibility of Results, alpha-Synuclein (cerebrospinal fluid).
- MESH :
- chemical , cerebrospinal fluid : alpha-Synuclein.
- cerebrospinal fluid : Alzheimer Disease, Lewy Body Disease, Neurodegenerative Diseases, Parkinson Disease.
- diagnosis : Alzheimer Disease, Lewy Body Disease, Neurodegenerative Diseases, Parkinson Disease.
- methods : Enzyme-Linked Immunosorbent Assay, Immunomagnetic Separation.
- standards : Enzyme-Linked Immunosorbent Assay, Immunomagnetic Separation.
- Adult, Aged, Aged, 80 and over, Feasibility Studies, Female, Humans, Male, Middle Aged, Reproducibility of Results.
Abstract
With the aim to evaluate the significance and reliability of detecting disease-specific α-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of α-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of β-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed α-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific α-synuclein was detectable in the CSF in a subset of patients with α-synuclein pathology in the brain. When combined with the analysis of total α-synuclein, the bead-assay for disease-specific α-synuclein was highly specific for PDD/DLB. Detection of disease-associated αsynuclein combined with the total levels of α-synuclein is a promising tool for the in-vivo diagnosis of α-synucleinopathies, including PDD and LBD.
PubMed: 25131945
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Berghoff</name></author><author><name sortKey="Flach, Katharina" sort="Flach, Katharina" uniqKey="Flach K" first="Katharina" last="Flach">Katharina Flach</name></author><author><name sortKey="Wagner, Uta" sort="Wagner, Uta" uniqKey="Wagner U" first="Uta" last="Wagner">Uta Wagner</name></author><author><name sortKey="Geneste, Aline" sort="Geneste, Aline" uniqKey="Geneste A" first="Aline" last="Geneste">Aline Geneste</name></author><author><name sortKey="Perret Liaudet, Armand" sort="Perret Liaudet, Armand" uniqKey="Perret Liaudet A" first="Armand" last="Perret-Liaudet">Armand Perret-Liaudet</name></author><author><name sortKey="Kovacs, Gabor G" sort="Kovacs, Gabor G" uniqKey="Kovacs G" first="Gabor G" last="Kovacs">Gabor G. 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Berghoff</name></author><author><name sortKey="Flach, Katharina" sort="Flach, Katharina" uniqKey="Flach K" first="Katharina" last="Flach">Katharina Flach</name></author><author><name sortKey="Wagner, Uta" sort="Wagner, Uta" uniqKey="Wagner U" first="Uta" last="Wagner">Uta Wagner</name></author><author><name sortKey="Geneste, Aline" sort="Geneste, Aline" uniqKey="Geneste A" first="Aline" last="Geneste">Aline Geneste</name></author><author><name sortKey="Perret Liaudet, Armand" sort="Perret Liaudet, Armand" uniqKey="Perret Liaudet A" first="Armand" last="Perret-Liaudet">Armand Perret-Liaudet</name></author><author><name sortKey="Kovacs, Gabor G" sort="Kovacs, Gabor G" uniqKey="Kovacs G" first="Gabor G" last="Kovacs">Gabor G. Kovacs</name></author></analytic><series><title level="j">Clinical neuropathology</title><idno type="ISSN">0722-5091</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Alzheimer Disease (cerebrospinal fluid)</term><term>Alzheimer Disease (diagnosis)</term><term>Enzyme-Linked Immunosorbent Assay (methods)</term><term>Enzyme-Linked Immunosorbent Assay (standards)</term><term>Feasibility Studies</term><term>Female</term><term>Humans</term><term>Immunomagnetic Separation (methods)</term><term>Immunomagnetic Separation (standards)</term><term>Lewy Body Disease (cerebrospinal fluid)</term><term>Lewy Body Disease (diagnosis)</term><term>Male</term><term>Middle Aged</term><term>Neurodegenerative Diseases (cerebrospinal fluid)</term><term>Neurodegenerative Diseases (diagnosis)</term><term>Parkinson Disease (cerebrospinal fluid)</term><term>Parkinson Disease (diagnosis)</term><term>Reproducibility of Results</term><term>alpha-Synuclein (cerebrospinal fluid)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="cerebrospinal fluid" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="cerebrospinal fluid" xml:lang="en"><term>Alzheimer Disease</term><term>Lewy Body Disease</term><term>Neurodegenerative Diseases</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Alzheimer Disease</term><term>Lewy Body Disease</term><term>Neurodegenerative Diseases</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Enzyme-Linked Immunosorbent Assay</term><term>Immunomagnetic Separation</term></keywords><keywords scheme="MESH" qualifier="standards" xml:lang="en"><term>Enzyme-Linked Immunosorbent Assay</term><term>Immunomagnetic Separation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Feasibility Studies</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Reproducibility of Results</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">With the aim to evaluate the significance and reliability of detecting disease-specific α-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of α-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of β-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed α-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific α-synuclein was detectable in the CSF in a subset of patients with α-synuclein pathology in the brain. When combined with the analysis of total α-synuclein, the bead-assay for disease-specific α-synuclein was highly specific for PDD/DLB. Detection of disease-associated αsynuclein combined with the total levels of α-synuclein is a promising tool for the in-vivo diagnosis of α-synucleinopathies, including PDD and LBD.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25131945</PMID><DateCreated><Year>2014</Year><Month>08</Month><Day>18</Day></DateCreated><DateCompleted><Year>2014</Year><Month>10</Month><Day>14</Day></DateCompleted><DateRevised><Year>2015</Year><Month>08</Month><Day>04</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0722-5091</ISSN><JournalIssue CitedMedium="Print"><Volume>33</Volume><Issue>5</Issue><PubDate><MedlineDate>2014 Sep-Oct</MedlineDate></PubDate></JournalIssue><Title>Clinical neuropathology</Title><ISOAbbreviation>Clin. Neuropathol.</ISOAbbreviation></Journal><ArticleTitle>Detection of disease-associated α-synuclein in the cerebrospinal fluid: a feasibility study.</ArticleTitle><Pagination><MedlinePgn>329-34</MedlinePgn></Pagination><Abstract><AbstractText>With the aim to evaluate the significance and reliability of detecting disease-specific α-synuclein in the cerebrospinal fluid (CSF) we developed an ELISA and bead-assay. We used a commercial antibody (5G4) that does not bind to the physiological monomeric form of α-synuclein, but is highly specific for the disease-associated forms, including high molecular weight fraction of β-sheet rich oligomers. We applied both tests in CSF from a series of neuropathologically confirmed α-synucleinopathy cases, including Parkinson' disease dementia (PDD) and dementia with Lewy bodies (DLB) (n = 7), as well as Alzheimer' disease (n = 6), and control patients without neurodegenerative pathologies (n = 9). Disease-specific α-synuclein was detectable in the CSF in a subset of patients with α-synuclein pathology in the brain. When combined with the analysis of total α-synuclein, the bead-assay for disease-specific α-synuclein was highly specific for PDD/DLB. Detection of disease-associated αsynuclein combined with the total levels of α-synuclein is a promising tool for the in-vivo diagnosis of α-synucleinopathies, including PDD and LBD.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Unterberger</LastName><ForeName>Ursula</ForeName><Initials>U</Initials><AffiliationInfo><Affiliation>Institute of Neurology, Medical University of Vienna, Vienna, Austria, AJ Roboscreen GmbH, Leipzig, Germany, Department of Neurology, present address: Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria, and Neurobiologie, CMRR, Hospices Civils de Lyon, Université Lyon, Lyon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lachmann</LastName><ForeName>Ingolf</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Voigtländer</LastName><ForeName>Till</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Pirker</LastName><ForeName>Walter</ForeName><Initials>W</Initials></Author><Author ValidYN="Y"><LastName>Berghoff</LastName><ForeName>Anna S</ForeName><Initials>AS</Initials></Author><Author ValidYN="Y"><LastName>Flach</LastName><ForeName>Katharina</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Wagner</LastName><ForeName>Uta</ForeName><Initials>U</Initials></Author><Author ValidYN="Y"><LastName>Geneste</LastName><ForeName>Aline</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Perret-Liaudet</LastName><ForeName>Armand</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Kovacs</LastName><ForeName>Gabor G</ForeName><Initials>GG</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016430">Clinical Trial</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D023361">Validation Studies</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Clin Neuropathol</MedlineTA><NlmUniqueID>8214420</NlmUniqueID><ISSNLinking>0722-5091</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497604">SNCA protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051844">alpha-Synuclein</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Neurobiol Dis. 2014 Sep;69:76-92</RefSource><PMID Version="1">24878508</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Acta Neuropathol. 2013 Nov;126(5):683-97</RefSource><PMID Version="1">23812319</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>PLoS One. 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Version="1">21317042</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neurology. 2010 Nov 16;75(20):1766-72</RefSource><PMID Version="1">20962290</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Clin Neuropathol. 2010 Sep-Oct;29(5):271-88</RefSource><PMID Version="1">20860890</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Acta Neuropathol. 2010 Apr;119(4):389-408</RefSource><PMID Version="1">20198481</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brain Res. 2009 Jan 28;1251:1-6</RefSource><PMID Version="1">19071095</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Neurol. 2008 Oct;213(2):315-25</RefSource><PMID Version="1">18625222</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Parkinsonism Relat Disord. 2007;13 Suppl 3:S457-61</RefSource><PMID Version="1">18267283</PMID></CommentsCorrections><CommentsCorrections 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MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000544" MajorTopicYN="N">Alzheimer Disease</DescriptorName><QualifierName UI="Q000134" MajorTopicYN="N">cerebrospinal fluid</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004797" MajorTopicYN="N">Enzyme-Linked Immunosorbent Assay</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005240" MajorTopicYN="N">Feasibility Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018189" MajorTopicYN="N">Immunomagnetic Separation</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName><QualifierName UI="Q000592" MajorTopicYN="N">standards</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020961" MajorTopicYN="N">Lewy Body Disease</DescriptorName><QualifierName UI="Q000134" MajorTopicYN="N">cerebrospinal fluid</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019636" MajorTopicYN="N">Neurodegenerative Diseases</DescriptorName><QualifierName UI="Q000134" MajorTopicYN="Y">cerebrospinal fluid</QualifierName><QualifierName UI="Q000175" MajorTopicYN="Y">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000134" MajorTopicYN="N">cerebrospinal fluid</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015203" MajorTopicYN="N">Reproducibility of Results</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051844" MajorTopicYN="N">alpha-Synuclein</DescriptorName><QualifierName UI="Q000134" MajorTopicYN="Y">cerebrospinal fluid</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC4151342</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>8</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>8</Month><Day>19</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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