Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies
Identifieur interne : 000892 ( Main/Exploration ); précédent : 000891; suivant : 000893Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies
Auteurs : Katerina E. Paleologou [Royaume-Uni] ; Christine L. Kragh [Danemark] ; David M. A. Mann [Royaume-Uni] ; Sultan A. Salem [Royaume-Uni] ; Rania Al-Shami [Émirats arabes unis] ; David Allsop [Royaume-Uni] ; Ahmed H. Hassan [Émirats arabes unis] ; Poul H. Jensen [Danemark] ; Omar M. A. El-Agnaf [Émirats arabes unis]Source :
- 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
Affiliations:
Links toward previous steps (curation, corpus...)
Le 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>
</author>
<author><name sortKey="Kragh, Christine L" sort="Kragh, Christine L" uniqKey="Kragh C" first="Christine L." last="Kragh">Christine L. Kragh</name>
</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>
</author>
<author><name sortKey="Salem, Sultan A" sort="Salem, Sultan A" uniqKey="Salem S" first="Sultan A." last="Salem">Sultan A. Salem</name>
</author>
<author><name sortKey="Al Shami, Rania" sort="Al Shami, Rania" uniqKey="Al Shami R" first="Rania" last="Al-Shami">Rania Al-Shami</name>
</author>
<author><name sortKey="Allsop, David" sort="Allsop, David" uniqKey="Allsop D" first="David" last="Allsop">David Allsop</name>
</author>
<author><name sortKey="Hassan, Ahmed H" sort="Hassan, Ahmed H" uniqKey="Hassan A" first="Ahmed H." last="Hassan">Ahmed H. Hassan</name>
</author>
<author><name sortKey="Jensen, Poul H" sort="Jensen, Poul H" uniqKey="Jensen P" first="Poul H." last="Jensen">Poul H. Jensen</name>
</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>
</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>
<idno type="wicri:Area/Main/Curation">001B19</idno>
<idno type="wicri:Area/Main/Exploration">000892</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ</wicri:regionArea>
<wicri:noRegion>Lancaster LA1 4YQ</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Danemark</country>
<wicri:regionArea>2 Institute of Medical Biochemistry, University of Aarhus</wicri:regionArea>
<wicri:noRegion>University of Aarhus</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>3 Clinical Neuroscience Research Group, School of Translational Medicine, University of Manchester Hope Hospital, Salford, M6 8HD</wicri:regionArea>
<wicri:noRegion>M6 8HD</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ</wicri:regionArea>
<wicri:noRegion>Lancaster LA1 4YQ</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Émirats arabes unis</country>
<wicri:regionArea>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain</wicri:regionArea>
<wicri:noRegion>Al Ain</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Allsop, David" sort="Allsop, David" uniqKey="Allsop D" first="David" last="Allsop">David Allsop</name>
<affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>1 Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ</wicri:regionArea>
<wicri:noRegion>Lancaster LA1 4YQ</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Émirats arabes unis</country>
<wicri:regionArea>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain</wicri:regionArea>
<wicri:noRegion>Al Ain</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Danemark</country>
<wicri:regionArea>2 Institute of Medical Biochemistry, University of Aarhus</wicri:regionArea>
<wicri:noRegion>University of Aarhus</wicri:noRegion>
</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 wicri:level="1"><country xml:lang="fr">Émirats arabes unis</country>
<wicri:regionArea>4 Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain</wicri:regionArea>
<wicri:noRegion>Al Ain</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><country wicri:rule="url">Émirats arabes unis</country>
</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>
<affiliations><list><country><li>Danemark</li>
<li>Royaume-Uni</li>
<li>Émirats arabes unis</li>
</country>
</list>
<tree><country name="Royaume-Uni"><noRegion><name sortKey="Paleologou, Katerina E" sort="Paleologou, Katerina E" uniqKey="Paleologou K" first="Katerina E." last="Paleologou">Katerina E. Paleologou</name>
</noRegion>
<name sortKey="Allsop, David" sort="Allsop, David" uniqKey="Allsop D" first="David" last="Allsop">David Allsop</name>
<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>
<name sortKey="Salem, Sultan A" sort="Salem, Sultan A" uniqKey="Salem S" first="Sultan A." last="Salem">Sultan A. Salem</name>
</country>
<country name="Danemark"><noRegion><name sortKey="Kragh, Christine L" sort="Kragh, Christine L" uniqKey="Kragh C" first="Christine L." last="Kragh">Christine L. Kragh</name>
</noRegion>
<name sortKey="Jensen, Poul H" sort="Jensen, Poul H" uniqKey="Jensen P" first="Poul H." last="Jensen">Poul H. Jensen</name>
</country>
<country name="Émirats arabes unis"><noRegion><name sortKey="Al Shami, Rania" sort="Al Shami, Rania" uniqKey="Al Shami R" first="Rania" last="Al-Shami">Rania Al-Shami</name>
</noRegion>
<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>
<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>
<name sortKey="Hassan, Ahmed H" sort="Hassan, Ahmed H" uniqKey="Hassan A" first="Ahmed H." last="Hassan">Ahmed H. Hassan</name>
</country>
</tree>
</affiliations>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000892 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000892 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonV1 |flux= Main |étape= Exploration |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. |