Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies
Identifieur interne : 001E04 ( Main/Corpus ); précédent : 001E03; suivant : 001E05Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies
Auteurs : Katerina E. Paleologou ; Christine L. Kragh ; David M. A. Mann ; Sultan A. Salem ; Rania Al-Shami ; David Allsop ; Ahmed H. Hassan ; Poul H. Jensen ; Omar M. A. El-AgnafSource :
- Brain [ 0006-8950 ] ; 2009-04.
Abstract
A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. These and other findings suggest that the accumulation of α-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or ‘soluble oligomers’ are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later ‘mature fibrils’. In this study, we investigated the presence of α-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble α-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to α-syn aggregates, but not to α-syn monomers, or to tau or β-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of α-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of α-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P < 0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of α-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of α-syn in human brain lysates.
Url:
DOI: 10.1093/brain/awn349
Links to Exploration step
ISTEX:585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8CLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title><author><name sortKey="Paleologou, Katerina E" sort="Paleologou, Katerina E" uniqKey="Paleologou K" first="Katerina E." last="Paleologou">Katerina E. Paleologou</name><affiliation><mods:affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</mods:affiliation></affiliation></author><author><name sortKey="Kragh, Christine L" sort="Kragh, Christine L" uniqKey="Kragh C" first="Christine L." last="Kragh">Christine L. Kragh</name><affiliation><mods:affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Mann, David M A" sort="Mann, David M A" uniqKey="Mann D" first="David M. A." last="Mann">David M. A. Mann</name><affiliation><mods:affiliation>3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD, UK</mods:affiliation></affiliation></author><author><name sortKey="Salem, Sultan A" sort="Salem, Sultan A" uniqKey="Salem S" first="Sultan A." last="Salem">Sultan A. Salem</name><affiliation><mods:affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</mods:affiliation></affiliation></author><author><name sortKey="Al Shami, Rania" sort="Al Shami, Rania" uniqKey="Al Shami R" first="Rania" last="Al-Shami">Rania Al-Shami</name><affiliation><mods:affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</mods:affiliation></affiliation></author><author><name sortKey="Allsop, David" sort="Allsop, David" uniqKey="Allsop D" first="David" last="Allsop">David Allsop</name><affiliation><mods:affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</mods:affiliation></affiliation></author><author><name sortKey="Hassan, Ahmed H" sort="Hassan, Ahmed H" uniqKey="Hassan A" first="Ahmed H." last="Hassan">Ahmed H. Hassan</name><affiliation><mods:affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</mods:affiliation></affiliation></author><author><name sortKey="Jensen, Poul H" sort="Jensen, Poul H" uniqKey="Jensen P" first="Poul H." last="Jensen">Poul H. Jensen</name><affiliation><mods:affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</mods:affiliation></affiliation></author><author><name sortKey="El Agnaf, Omar M A" sort="El Agnaf, Omar M A" uniqKey="El Agnaf O" first="Omar M. A." last="El-Agnaf">Omar M. A. El-Agnaf</name><affiliation><mods:affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: o.elagnaf@uaeu.ac.ae</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1093/brain/awn349</idno><idno type="url">https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001E04</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title><author><name sortKey="Paleologou, Katerina E" sort="Paleologou, Katerina E" uniqKey="Paleologou K" first="Katerina E." last="Paleologou">Katerina E. Paleologou</name><affiliation><mods:affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</mods:affiliation></affiliation></author><author><name sortKey="Kragh, Christine L" sort="Kragh, Christine L" uniqKey="Kragh C" first="Christine L." last="Kragh">Christine L. Kragh</name><affiliation><mods:affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</mods:affiliation></affiliation></author><author><name sortKey="Mann, David M A" sort="Mann, David M A" uniqKey="Mann D" first="David M. A." last="Mann">David M. A. Mann</name><affiliation><mods:affiliation>3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD, UK</mods:affiliation></affiliation></author><author><name sortKey="Salem, Sultan A" sort="Salem, Sultan A" uniqKey="Salem S" first="Sultan A." last="Salem">Sultan A. Salem</name><affiliation><mods:affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</mods:affiliation></affiliation></author><author><name sortKey="Al Shami, Rania" sort="Al Shami, Rania" uniqKey="Al Shami R" first="Rania" last="Al-Shami">Rania Al-Shami</name><affiliation><mods:affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</mods:affiliation></affiliation></author><author><name sortKey="Allsop, David" sort="Allsop, David" uniqKey="Allsop D" first="David" last="Allsop">David Allsop</name><affiliation><mods:affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</mods:affiliation></affiliation></author><author><name sortKey="Hassan, Ahmed H" sort="Hassan, Ahmed H" uniqKey="Hassan A" first="Ahmed H." last="Hassan">Ahmed H. Hassan</name><affiliation><mods:affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</mods:affiliation></affiliation></author><author><name sortKey="Jensen, Poul H" sort="Jensen, Poul H" uniqKey="Jensen P" first="Poul H." last="Jensen">Poul H. Jensen</name><affiliation><mods:affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</mods:affiliation></affiliation></author><author><name sortKey="El Agnaf, Omar M A" sort="El Agnaf, Omar M A" uniqKey="El Agnaf O" first="Omar M. A." last="El-Agnaf">Omar M. A. El-Agnaf</name><affiliation><mods:affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: o.elagnaf@uaeu.ac.ae</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-04">2009-04</date><biblScope unit="volume">132</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="1093">1093</biblScope><biblScope unit="page" to="1101">1101</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C</idno><idno type="DOI">10.1093/brain/awn349</idno><idno type="ArticleID">awn349</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. These and other findings suggest that the accumulation of α-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or ‘soluble oligomers’ are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later ‘mature fibrils’. In this study, we investigated the presence of α-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble α-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to α-syn aggregates, but not to α-syn monomers, or to tau or β-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of α-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of α-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P < 0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of α-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of α-syn in human brain lysates.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Katerina E. Paleologou</name><affiliations><json:string>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</json:string></affiliations></json:item><json:item><name>Christine L. Kragh</name><affiliations><json:string>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</json:string></affiliations></json:item><json:item><name>David M. A. Mann</name><affiliations><json:string>3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD, UK</json:string></affiliations></json:item><json:item><name>Sultan A. Salem</name><affiliations><json:string>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</json:string></affiliations></json:item><json:item><name>Rania Al-Shami</name><affiliations><json:string>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</json:string></affiliations></json:item><json:item><name>David Allsop</name><affiliations><json:string>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</json:string></affiliations></json:item><json:item><name>Ahmed H. Hassan</name><affiliations><json:string>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</json:string></affiliations></json:item><json:item><name>Poul H. Jensen</name><affiliations><json:string>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</json:string></affiliations></json:item><json:item><name>Omar M. A. El-Agnaf</name><affiliations><json:string>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</json:string><json:string>E-mail: o.elagnaf@uaeu.ac.ae</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Original Articles</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dementia with Lewy bodies</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>neurodegeneration</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>amyloid oligomers</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>α-synuclein</value></json:item></subject><language><json:string>eng</json:string></language><abstract>A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. These and other findings suggest that the accumulation of α-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or ‘soluble oligomers’ are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later ‘mature fibrils’. In this study, we investigated the presence of α-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble α-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to α-syn aggregates, but not to α-syn monomers, or to tau or β-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of α-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of α-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P > 0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of α-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of α-syn in human brain lysates.</abstract><qualityIndicators><score>8.5</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612.68 x 790.866 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>1707</abstractCharCount><pdfWordCount>6440</pdfWordCount><pdfCharCount>39435</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>255</abstractWordCount></qualityIndicators><title>Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title><genre><json:string>research-article</json:string></genre><host><volume>132</volume><pages><last>1101</last><first>1093</first></pages><issn><json:string>0006-8950</json:string></issn><issue>4</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1460-2156</json:string></eissn><title>Brain</title></host><categories><wos><json:string>CLINICAL NEUROLOGY</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><doi><json:string>10.1093/brain/awn349</json:string></doi><id>585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2009-01-20</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title><author><persName><forename type="first">Katerina E.</forename><surname>Paleologou</surname></persName><affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</affiliation></author><author><persName><forename type="first">Christine L.</forename><surname>Kragh</surname></persName><affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</affiliation></author><author><persName><forename type="first">David M. A.</forename><surname>Mann</surname></persName><affiliation>3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD, UK</affiliation></author><author><persName><forename type="first">Sultan A.</forename><surname>Salem</surname></persName><affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</affiliation></author><author><persName><forename type="first">Rania</forename><surname>Al-Shami</surname></persName><affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</affiliation></author><author><persName><forename type="first">David</forename><surname>Allsop</surname></persName><affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</affiliation></author><author><persName><forename type="first">Ahmed H.</forename><surname>Hassan</surname></persName><affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</affiliation></author><author><persName><forename type="first">Poul H.</forename><surname>Jensen</surname></persName><affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</affiliation></author><author corresp="yes"><persName><forename type="first">Omar M. A.</forename><surname>El-Agnaf</surname></persName><email>o.elagnaf@uaeu.ac.ae</email><affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</affiliation></author></analytic><monogr><title level="j">Brain</title><idno type="pISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-04"></date><biblScope unit="volume">132</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="1093">1093</biblScope><biblScope unit="page" to="1101">1101</biblScope></imprint></monogr><idno type="istex">585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C</idno><idno type="DOI">10.1093/brain/awn349</idno><idno type="ArticleID">awn349</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2009-01-20</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. These and other findings suggest that the accumulation of α-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or ‘soluble oligomers’ are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later ‘mature fibrils’. In this study, we investigated the presence of α-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble α-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to α-syn aggregates, but not to α-syn monomers, or to tau or β-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of α-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of α-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P < 0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of α-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of α-syn in human brain lysates.</p></abstract><textClass><keywords scheme="keyword"><list><item><term>Original Articles</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>dementia with Lewy bodies</term></item><item><term>neurodegeneration</term></item><item><term>amyloid oligomers</term></item><item><term>α-synuclein</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2009-01-20">Created</change><change when="2009-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article"><front><journal-meta><journal-id journal-id-type="hwp">brain</journal-id><journal-id journal-id-type="publisher-id">brainj</journal-id><journal-title>Brain</journal-title><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="doi">10.1093/brain/awn349</article-id><article-id pub-id-type="publisher-id">awn349</article-id><article-categories><subj-group><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Paleologou</surname><given-names>Katerina E.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kragh</surname><given-names>Christine L.</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mann</surname><given-names>David M. A.</given-names></name><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Salem</surname><given-names>Sultan A.</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Al-Shami</surname><given-names>Rania</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Allsop</surname><given-names>David</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hassan</surname><given-names>Ahmed H.</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jensen</surname><given-names>Poul H.</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>El-Agnaf</surname><given-names>Omar M. A.</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref></contrib></contrib-group><aff id="AFF1">1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</aff><aff id="AFF2">2 Institute of Medical Biochemistry, University of Aarhus, Denmark</aff><aff id="AFF3">3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD, UK</aff><aff id="AFF4">4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</aff><author-notes><corresp>Correspondence to: Dr Omar M. El-Agnaf, Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates E-mail: <email>o.elagnaf@uaeu.ac.ae</email></corresp></author-notes><pub-date pub-type="ppub"><month>4</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>20</day><month>1</month><year>2009</year></pub-date><volume>132</volume><issue>4</issue><fpage>1093</fpage><lpage>1101</lpage><history><date date-type="received"><day>8</day><month>8</month><year>2008</year></date><date date-type="rev-recd"><day>18</day><month>11</month><year>2008</year></date><date date-type="accepted"><day>19</day><month>11</month><year>2008</year></date></history><permissions><copyright-statement>© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</copyright-statement><copyright-year>2009</copyright-year></permissions><abstract><p>A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. These and other findings suggest that the accumulation of α-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or ‘soluble oligomers’ are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later ‘mature fibrils’. In this study, we investigated the presence of α-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble α-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to α-syn aggregates, but not to α-syn monomers, or to tau or β-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of α-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of α-syn in the DLB brains compared to those with Alzheimer's disease and the controls (<italic>P</italic> < 0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of α-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of α-syn in human brain lysates.</p></abstract><kwd-group><kwd>dementia with Lewy bodies</kwd><kwd>neurodegeneration</kwd><kwd>amyloid oligomers</kwd><kwd>α-synuclein</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies</title></titleInfo><name type="personal"><namePart type="given">Katerina E.</namePart><namePart type="family">Paleologou</namePart><affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christine L.</namePart><namePart type="family">Kragh</namePart><affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David M. A.</namePart><namePart type="family">Mann</namePart><affiliation>3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sultan A.</namePart><namePart type="family">Salem</namePart><affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rania</namePart><namePart type="family">Al-Shami</namePart><affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Allsop</namePart><affiliation>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ahmed H.</namePart><namePart type="family">Hassan</namePart><affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Poul H.</namePart><namePart type="family">Jensen</namePart><affiliation>2 Institute of Medical Biochemistry, University of Aarhus, Denmark</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Omar M. A.</namePart><namePart type="family">El-Agnaf</namePart><affiliation>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates</affiliation><affiliation>E-mail: o.elagnaf@uaeu.ac.ae</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article"></genre><subject><topic>Original Articles</topic></subject><originInfo><publisher>Oxford University Press</publisher><dateIssued encoding="w3cdtf">2009-04</dateIssued><dateCreated encoding="w3cdtf">2009-01-20</dateCreated><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>A number of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of α-synuclein (α-syn) protein in affected brain regions. These and other findings suggest that the accumulation of α-syn in the brain plays an important role in the pathogenesis of these diseases. However, more recently it has been reported that early amyloid aggregates or ‘soluble oligomers’ are the pathogenic species that lead to neurodegeneration and neuronal cell death rather than the later ‘mature fibrils’. In this study, we investigated the presence of α-syn oligomers in brain lysates prepared from frozen post-mortem brains of normal, Alzheimer's disease and DLB patients. The brain extracts were subjected to high speed centrifugation, to remove insoluble α-syn aggregates, followed by specific detection of soluble oligomers in the supernatants by employing FILA-1, an antibody that specifically binds to α-syn aggregates, but not to α-syn monomers, or to tau or β-amyloid aggregates. Using this novel enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of α-syn oligomers in the brain extracts, our data clearly show an increase in the levels of soluble oligomers of α-syn in the DLB brains compared to those with Alzheimer's disease and the controls (P < 0.0001). Our findings provide strong evidence to support the contention that elevated soluble oligomers of α-syn are involved in the pathogenesis of DLB. Furthermore, these findings establish FILA-1 as a very sensitive tool for the detection of oligomeric forms of α-syn in human brain lysates.</abstract><subject><genre>Keywords</genre><topic>dementia with Lewy bodies</topic><topic>neurodegeneration</topic><topic>amyloid oligomers</topic><topic>α-synuclein</topic></subject><relatedItem type="host"><titleInfo><title>Brain</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0006-8950</identifier><identifier type="eISSN">1460-2156</identifier><identifier type="PublisherID">brainj</identifier><identifier type="PublisherID-hwp">brain</identifier><part><date>2009</date><detail type="volume"><caption>vol.</caption><number>132</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>1093</start><end>1101</end></extent></part></relatedItem><identifier type="istex">585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C</identifier><identifier type="DOI">10.1093/brain/awn349</identifier><identifier type="ArticleID">awn349</identifier><accessCondition type="use and reproduction" contentType="copyright">© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org</accessCondition><recordInfo><recordContentSource>OUP</recordContentSource></recordInfo></mods></metadata><covers><json:item><original>true</original><mimetype>image/tiff</mimetype><extension>tiff</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/covers/tiff</uri></json:item><json:item><original>true</original><mimetype>text/html</mimetype><extension>html</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/covers/html</uri></json:item></covers><annexes><json:item><original>true</original><mimetype>image/jpeg</mimetype><extension>jpeg</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/annexes/jpeg</uri></json:item><json:item><original>true</original><mimetype>image/gif</mimetype><extension>gif</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/annexes/gif</uri></json:item><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/annexes/pdf</uri></json:item></annexes><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">CLINICAL NEUROLOGY</classCode><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001E04 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 001E04 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:585BEE8F851A1E38CD9AC5E5A3EEF40BA568EB8C
|texte= Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies
}}
| This area was generated with Dilib version V0.6.23. |  |