The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies
Identifieur interne : 000394 ( Main/Corpus ); précédent : 000393; suivant : 000395The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies
Auteurs : Katrin Beyer ; Montserrat Domingo-Sbat ; Cristina Santos ; Eduardo Tolosa ; Isidro Ferrer ; Aurelio ArizaSource :
- Brain [ 0006-8950 ] ; 2010-12.
Abstract
Lewy body diseases include dementia with Lewy bodies and Parkinsons disease. Whereas dementia with Lewy bodies and Parkinsons disease can be distinguished as separate clinical entities, the pathological picture is very often identical. -synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and -synuclein inhibits -synuclein aggregation in vitro and in vivo. Recently, -synuclein has been shown to interact directly with -synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two -synuclein transcript variants and the main -synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimers disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimers disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the Ct method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of -synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimers disease pathology or the clinical phenotype of Parkinsons disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of -synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.
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DOI: 10.1093/brain/awq275
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Trias i Pujol, Universidad Autonoma de Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Santos, Cristina" sort="Santos, Cristina" uniqKey="Santos C" first="Cristina" last="Santos">Cristina Santos</name><affiliation><mods:affiliation>3 Unitat d'Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Tolosa, Eduardo" sort="Tolosa, Eduardo" uniqKey="Tolosa E" first="Eduardo" last="Tolosa">Eduardo Tolosa</name><affiliation><mods:affiliation>4 Servicio de Neurologa, Centro de Investigacin en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clnic, Universidad de Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Ferrer, Isidro" sort="Ferrer, Isidro" uniqKey="Ferrer I" first="Isidro" last="Ferrer">Isidro Ferrer</name><affiliation><mods:affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Ariza, Aurelio" sort="Ariza, Aurelio" uniqKey="Ariza A" first="Aurelio" last="Ariza">Aurelio Ariza</name><affiliation><mods:affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:6BBF9B326D67DFDB7F8C32E63533539F3BA561DB</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1093/brain/awq275</idno><idno type="url">https://api.istex.fr/document/6BBF9B326D67DFDB7F8C32E63533539F3BA561DB/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000394</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</title><author><name sortKey="Beyer, Katrin" sort="Beyer, Katrin" uniqKey="Beyer K" first="Katrin" last="Beyer">Katrin Beyer</name><affiliation><mods:affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: katrinbeyer@hotmail.com</mods:affiliation></affiliation></author><author><name sortKey="Domingo Sbat, Montserrat" sort="Domingo Sbat, Montserrat" uniqKey="Domingo Sbat M" first="Montserrat" last="Domingo-Sbat">Montserrat Domingo-Sbat</name><affiliation><mods:affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Santos, Cristina" sort="Santos, Cristina" uniqKey="Santos C" first="Cristina" last="Santos">Cristina Santos</name><affiliation><mods:affiliation>3 Unitat d'Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Tolosa, Eduardo" sort="Tolosa, Eduardo" uniqKey="Tolosa E" first="Eduardo" last="Tolosa">Eduardo Tolosa</name><affiliation><mods:affiliation>4 Servicio de Neurologa, Centro de Investigacin en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clnic, Universidad de Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Ferrer, Isidro" sort="Ferrer, Isidro" uniqKey="Ferrer I" first="Isidro" last="Ferrer">Isidro Ferrer</name><affiliation><mods:affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</mods:affiliation></affiliation></author><author><name sortKey="Ariza, Aurelio" sort="Ariza, Aurelio" uniqKey="Ariza A" first="Aurelio" last="Ariza">Aurelio Ariza</name><affiliation><mods:affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</mods:affiliation></affiliation><affiliation><mods:affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</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="2010-12">2010-12</date><biblScope unit="volume">133</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="3724">3724</biblScope><biblScope unit="page" to="3733">3733</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">6BBF9B326D67DFDB7F8C32E63533539F3BA561DB</idno><idno type="DOI">10.1093/brain/awq275</idno><idno 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Whereas dementia with Lewy bodies and Parkinsons disease can be distinguished as separate clinical entities, the pathological picture is very often identical. -synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and -synuclein inhibits -synuclein aggregation in vitro and in vivo. Recently, -synuclein has been shown to interact directly with -synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two -synuclein transcript variants and the main -synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimers disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimers disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the Ct method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of -synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimers disease pathology or the clinical phenotype of Parkinsons disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of -synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Katrin Beyer</name><affiliations><json:string>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</json:string><json:string>2 ICS Institute of Neuropathology, Barcelona, Spain</json:string><json:string>E-mail: katrinbeyer@hotmail.com</json:string></affiliations></json:item><json:item><name>Montserrat Domingo-Sbat</name><affiliations><json:string>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</json:string></affiliations></json:item><json:item><name>Cristina Santos</name><affiliations><json:string>3 Unitat d'Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, Spain</json:string></affiliations></json:item><json:item><name>Eduardo Tolosa</name><affiliations><json:string>4 Servicio de Neurologa, Centro de Investigacin en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clnic, Universidad de Barcelona, Spain</json:string></affiliations></json:item><json:item><name>Isidro Ferrer</name><affiliations><json:string>2 ICS Institute of Neuropathology, Barcelona, Spain</json:string></affiliations></json:item><json:item><name>Aurelio Ariza</name><affiliations><json:string>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</json:string><json:string>2 ICS Institute of Neuropathology, Barcelona, Spain</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>-synuclein</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>-synuclein</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>differential isoform expression</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>mRNA expression</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Lewy body diseases include dementia with Lewy bodies and Parkinsons disease. Whereas dementia with Lewy bodies and Parkinsons disease can be distinguished as separate clinical entities, the pathological picture is very often identical. -synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and -synuclein inhibits -synuclein aggregation in vitro and in vivo. Recently, -synuclein has been shown to interact directly with -synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two -synuclein transcript variants and the main -synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimers disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimers disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the Ct method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of -synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimers disease pathology or the clinical phenotype of Parkinsons disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of -synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.</abstract><qualityIndicators><score>8.5</score><pdfVersion>1.4</pdfVersion><pdfPageSize>612.68 x 790.866 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>2018</abstractCharCount><pdfWordCount>6214</pdfWordCount><pdfCharCount>42761</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>286</abstractWordCount></qualityIndicators><title>The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</title><genre><json:string>research-article</json:string></genre><host><volume>133</volume><pages><last>3733</last><first>3724</first></pages><issn><json:string>0006-8950</json:string></issn><issue>12</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>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1093/brain/awq275</json:string></doi><id>6BBF9B326D67DFDB7F8C32E63533539F3BA561DB</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/6BBF9B326D67DFDB7F8C32E63533539F3BA561DB/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/6BBF9B326D67DFDB7F8C32E63533539F3BA561DB/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/6BBF9B326D67DFDB7F8C32E63533539F3BA561DB/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><p>OUP</p></availability><date>2010-10-19</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</title><author corresp="yes"><persName><forename type="first">Katrin</forename><surname>Beyer</surname></persName><email>katrinbeyer@hotmail.com</email><affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</affiliation><affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</affiliation></author><author><persName><forename type="first">Montserrat</forename><surname>Domingo-Sbat</surname></persName><affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</affiliation></author><author><persName><forename type="first">Cristina</forename><surname>Santos</surname></persName><affiliation>3 Unitat d'Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, Spain</affiliation></author><author><persName><forename type="first">Eduardo</forename><surname>Tolosa</surname></persName><affiliation>4 Servicio de Neurologa, Centro de Investigacin en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clnic, Universidad de Barcelona, Spain</affiliation></author><author><persName><forename type="first">Isidro</forename><surname>Ferrer</surname></persName><affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</affiliation></author><author><persName><forename type="first">Aurelio</forename><surname>Ariza</surname></persName><affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</affiliation><affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</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="2010-12"></date><biblScope unit="volume">133</biblScope><biblScope unit="issue">12</biblScope><biblScope unit="page" from="3724">3724</biblScope><biblScope unit="page" to="3733">3733</biblScope></imprint></monogr><idno type="istex">6BBF9B326D67DFDB7F8C32E63533539F3BA561DB</idno><idno type="DOI">10.1093/brain/awq275</idno><idno type="ArticleID">awq275</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010-10-19</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Lewy body diseases include dementia with Lewy bodies and Parkinsons disease. Whereas dementia with Lewy bodies and Parkinsons disease can be distinguished as separate clinical entities, the pathological picture is very often identical. -synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and -synuclein inhibits -synuclein aggregation in vitro and in vivo. Recently, -synuclein has been shown to interact directly with -synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two -synuclein transcript variants and the main -synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimers disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimers disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the Ct method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of -synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimers disease pathology or the clinical phenotype of Parkinsons disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of -synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.</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>-synuclein</term></item><item><term>-synuclein</term></item><item><term>dementia with Lewy bodies</term></item><item><term>differential isoform expression</term></item><item><term>mRNA expression</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-10-19">Created</change><change when="2010-12">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/6BBF9B326D67DFDB7F8C32E63533539F3BA561DB/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="publisher-id">brainj</journal-id><journal-id journal-id-type="hwp">brain</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/awq275</article-id><article-id pub-id-type="publisher-id">awq275</article-id><article-categories><subj-group><subject>Original Articles</subject></subj-group></article-categories><title-group><article-title>The decrease of β-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Beyer</surname><given-names>Katrin</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Domingo-Sàbat</surname><given-names>Montserrat</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Santos</surname><given-names>Cristina</given-names></name><xref ref-type="aff" rid="AFF3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tolosa</surname><given-names>Eduardo</given-names></name><xref ref-type="aff" rid="AFF4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ferrer</surname><given-names>Isidro</given-names></name><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ariza</surname><given-names>Aurelio</given-names></name><xref ref-type="aff" rid="AFF1"><sup>1</sup></xref><xref ref-type="aff" rid="AFF2"><sup>2</sup></xref></contrib></contrib-group><aff id="AFF1">1 Servicio de Anatomía Patológica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</aff><aff id="AFF2">2 ICS Institute of Neuropathology, Barcelona, Spain</aff><aff id="AFF3">3 Unitat d'Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, Spain</aff><aff id="AFF4">4 Servicio de Neurología, Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, Universidad de Barcelona, Spain</aff><author-notes><corresp>Correspondence to: Dr Katrin Beyer, Servicio de Anatomía Patológica, Hospital Universitario Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain E-mail: <email>katrinbeyer@hotmail.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>12</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>19</day><month>10</month><year>2010</year></pub-date><volume>133</volume><issue>12</issue><fpage>3724</fpage><lpage>3733</lpage><history><date date-type="received"><day>5</day><month>3</month><year>2010</year></date><date date-type="rev-recd"><day>27</day><month>7</month><year>2010</year></date><date date-type="accepted"><day>9</day><month>8</month><year>2010</year></date></history><permissions><copyright-statement>© The Author (2010). 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>2010</copyright-year></permissions><abstract><p>Lewy body diseases include dementia with Lewy bodies and Parkinson’s disease. Whereas dementia with Lewy bodies and Parkinson’s disease can be distinguished as separate clinical entities, the pathological picture is very often identical. α-synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and β-synuclein inhibits α-synuclein aggregation <italic>in vitro</italic> and <italic>in vivo</italic>. Recently, β-synuclein has been shown to interact directly with α-synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two β-synuclein transcript variants and the main α-synuclein transcript <italic>SNCA140</italic>, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimer’s disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimer’s disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the ΔΔ<italic>C</italic><sub>t</sub> method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of β-synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimer’s disease pathology or the clinical phenotype of Parkinson’s disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of β-synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.</p></abstract><kwd-group><kwd>β-synuclein</kwd><kwd>α-synuclein</kwd><kwd>dementia with Lewy bodies</kwd><kwd>differential isoform expression</kwd><kwd>mRNA expression</kwd></kwd-group></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>The decrease of -synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Katrin</namePart><namePart type="family">Beyer</namePart><affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</affiliation><affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</affiliation><affiliation>E-mail: katrinbeyer@hotmail.com</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Montserrat</namePart><namePart type="family">Domingo-Sbat</namePart><affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cristina</namePart><namePart type="family">Santos</namePart><affiliation>3 Unitat d'Antropologia Biologica, Departament de Biologia Animal, Biologia Vegetal i Ecologia, Universitat Autonoma de Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eduardo</namePart><namePart type="family">Tolosa</namePart><affiliation>4 Servicio de Neurologa, Centro de Investigacin en Red de Enfermedades Neurodegenerativas (CIBERNED), Hospital Clnic, Universidad de Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Isidro</namePart><namePart type="family">Ferrer</namePart><affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Aurelio</namePart><namePart type="family">Ariza</namePart><affiliation>1 Servicio de Anatoma Patolgica, Hospital Universitario Germans Trias i Pujol, Universidad Autonoma de Barcelona, Spain</affiliation><affiliation>2 ICS Institute of Neuropathology, Barcelona, Spain</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">2010-12</dateIssued><dateCreated encoding="w3cdtf">2010-10-19</dateCreated><copyrightDate encoding="w3cdtf">2010</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>Lewy body diseases include dementia with Lewy bodies and Parkinsons disease. Whereas dementia with Lewy bodies and Parkinsons disease can be distinguished as separate clinical entities, the pathological picture is very often identical. -synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and -synuclein inhibits -synuclein aggregation in vitro and in vivo. Recently, -synuclein has been shown to interact directly with -synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two -synuclein transcript variants and the main -synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimers disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimers disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the Ct method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of -synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimers disease pathology or the clinical phenotype of Parkinsons disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of -synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of molecular mechanisms involved in these complex diseases.</abstract><subject><genre>Keywords</genre><topic>-synuclein</topic><topic>-synuclein</topic><topic>dementia with Lewy bodies</topic><topic>differential isoform expression</topic><topic>mRNA expression</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>2010</date><detail type="volume"><caption>vol.</caption><number>133</number></detail><detail type="issue"><caption>no.</caption><number>12</number></detail><extent unit="pages"><start>3724</start><end>3733</end></extent></part></relatedItem><identifier type="istex">6BBF9B326D67DFDB7F8C32E63533539F3BA561DB</identifier><identifier type="DOI">10.1093/brain/awq275</identifier><identifier type="ArticleID">awq275</identifier><accessCondition type="use and reproduction" contentType="copyright">The Author (2010). 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