First appraisal of brain pathology owing to A30P mutant alpha‐synuclein
Identifieur interne : 002D78 ( Main/Corpus ); précédent : 002D77; suivant : 002D79First appraisal of brain pathology owing to A30P mutant alpha‐synuclein
Auteurs : Kay Seidel ; Ludger Schöls ; Silke Nuber ; Elisabeth Petrasch-Parwez ; Kristin Gierga ; Zbigniew Wszolek ; Dennis Dickson ; Wei P. Gai ; Antje Bornemann ; Olaf Riess ; Abdelhaq Rami ; Wilfried F. A. Den Dunnen ; Thomas Deller ; Udo Rüb ; Rejko KrügerSource :
- Annals of Neurology [ 0364-5134 ] ; 2010-05.
Abstract
Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha‐synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha‐synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha‐synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha‐synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684–689
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DOI: 10.1002/ana.21966
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Gai</name><affiliation><mods:affiliation>Department of Human Physiology, Flinders University School of Medicine, Bedford Park, Australia</mods:affiliation></affiliation></author><author><name sortKey="Bornemann, Antje" sort="Bornemann, Antje" uniqKey="Bornemann A" first="Antje" last="Bornemann">Antje Bornemann</name><affiliation><mods:affiliation>Institute of Brain Research, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Riess, Olaf" sort="Riess, Olaf" uniqKey="Riess O" first="Olaf" last="Riess">Olaf Riess</name><affiliation><mods:affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Rami, Abdelhaq" sort="Rami, Abdelhaq" uniqKey="Rami A" first="Abdelhaq" last="Rami">Abdelhaq Rami</name><affiliation><mods:affiliation>Institute for Cellular and Molecular Anatomy, Goethe University, Frankfurt am Main, Germany</mods:affiliation></affiliation></author><author><name sortKey="Den Dunnen, Wilfried F A" sort="Den Dunnen, Wilfried F A" uniqKey="Den Dunnen W" first="Wilfried F. A." last="Den Dunnen">Wilfried F. A. Den Dunnen</name><affiliation><mods:affiliation>Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Deller, Thomas" sort="Deller, Thomas" uniqKey="Deller T" first="Thomas" last="Deller">Thomas Deller</name><affiliation><mods:affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</mods:affiliation></affiliation></author><author><name sortKey="Rub, Udo" sort="Rub, Udo" uniqKey="Rub U" first="Udo" last="Rüb">Udo Rüb</name><affiliation><mods:affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kruger, Rejko" sort="Kruger, Rejko" uniqKey="Kruger R" first="Rejko" last="Krüger">Rejko Krüger</name><affiliation><mods:affiliation>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-05">2010-05</date><biblScope unit="volume">67</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="684">684</biblScope><biblScope unit="page" to="689">689</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B</idno><idno type="DOI">10.1002/ana.21966</idno><idno type="ArticleID">ANA21966</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha‐synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha‐synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha‐synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha‐synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684–689</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Kay Seidel PhD</name><affiliations><json:string>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</json:string></affiliations></json:item><json:item><name>Ludger Schöls MD</name><affiliations><json:string>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Silke Nuber PhD</name><affiliations><json:string>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Elisabeth Petrasch‐Parwez MD</name><affiliations><json:string>Neuroanatomy and Molecular Brain Research, Ruhr‐University Bochum, Bochum, Germany</json:string></affiliations></json:item><json:item><name>Kristin Gierga MD</name><affiliations><json:string>Department of Neuropathology, Heinrich‐Heine‐University, Düsseldorf, Germany</json:string></affiliations></json:item><json:item><name>Zbigniew Wszolek MD</name><affiliations><json:string>Department of Neurology, Mayo Clinic, Jacksonville, FL</json:string></affiliations></json:item><json:item><name>Dennis Dickson MD</name><affiliations><json:string>Neuropathology Laboratory, Mayo Clinic, Jacksonville, FL</json:string></affiliations></json:item><json:item><name>Wei P. Gai PhD, MD</name><affiliations><json:string>Department of Human Physiology, Flinders University School of Medicine, Bedford Park, Australia</json:string></affiliations></json:item><json:item><name>Antje Bornemann MD</name><affiliations><json:string>Institute of Brain Research, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Olaf Riess MD</name><affiliations><json:string>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Abdelhaq Rami PhD</name><affiliations><json:string>Institute for Cellular and Molecular Anatomy, Goethe University, Frankfurt am Main, Germany</json:string></affiliations></json:item><json:item><name>Wilfried F. A. Den Dunnen MD</name><affiliations><json:string>Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</json:string></affiliations></json:item><json:item><name>Thomas Deller MD</name><affiliations><json:string>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</json:string></affiliations></json:item><json:item><name>Udo Rüb MD</name><affiliations><json:string>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</json:string><json:string>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</json:string></affiliations></json:item><json:item><name>Rejko Krüger MD</name><affiliations><json:string>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</json:string><json:string>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</json:string></affiliations></json:item></author><articleId><json:string>ANA21966</json:string></articleId><language><json:string>eng</json:string></language><abstract>Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha‐synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha‐synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha‐synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha‐synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684–689</abstract><qualityIndicators><score>4.383</score><pdfVersion>1.3</pdfVersion><pdfPageSize>594 x 783 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>758</abstractCharCount><pdfWordCount>3171</pdfWordCount><pdfCharCount>21791</pdfCharCount><pdfPageCount>6</pdfPageCount><abstractWordCount>101</abstractWordCount></qualityIndicators><title>First appraisal of brain pathology owing to A30P mutant alpha‐synuclein</title><genre><json:string>brief communication</json:string></genre><host><volume>67</volume><publisherId><json:string>ANA</json:string></publisherId><pages><total>6</total><last>689</last><first>684</first></pages><issn><json:string>0364-5134</json:string></issn><issue>5</issue><subject><json:item><value>Brief Communication</value></json:item></subject><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1531-8249</json:string></eissn><title>Annals of Neurology</title><doi><json:string>10.1002/(ISSN)1531-8249</json:string></doi></host><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1002/ana.21966</json:string></doi><id>7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">First appraisal of brain pathology owing to A30P mutant alpha‐synuclein</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>WILEY</p></availability><date>2010</date></publicationStmt><notesStmt><note>Deutsche Forschungsgemeinschaft - No. RU 1215/1‐2; No. KR2119/3‐1;</note><note>Federal Ministry for Education and Research - No. 01GS01834;</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">First appraisal of brain pathology owing to A30P mutant alpha‐synuclein</title><author><persName><forename type="first">Kay</forename><surname>Seidel</surname></persName><roleName type="degree">PhD</roleName><affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation></author><author><persName><forename type="first">Ludger</forename><surname>Schöls</surname></persName><roleName type="degree">MD</roleName><affiliation>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Silke</forename><surname>Nuber</surname></persName><roleName type="degree">PhD</roleName><affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Elisabeth</forename><surname>Petrasch‐Parwez</surname></persName><roleName type="degree">MD</roleName><affiliation>Neuroanatomy and Molecular Brain Research, Ruhr‐University Bochum, Bochum, Germany</affiliation></author><author><persName><forename type="first">Kristin</forename><surname>Gierga</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neuropathology, Heinrich‐Heine‐University, Düsseldorf, Germany</affiliation></author><author><persName><forename type="first">Zbigniew</forename><surname>Wszolek</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, Mayo Clinic, Jacksonville, FL</affiliation></author><author><persName><forename type="first">Dennis</forename><surname>Dickson</surname></persName><roleName type="degree">MD</roleName><affiliation>Neuropathology Laboratory, Mayo Clinic, Jacksonville, FL</affiliation></author><author><persName><forename type="first">Wei P.</forename><surname>Gai</surname></persName><roleName type="degree">PhD, MD</roleName><affiliation>Department of Human Physiology, Flinders University School of Medicine, Bedford Park, Australia</affiliation></author><author><persName><forename type="first">Antje</forename><surname>Bornemann</surname></persName><roleName type="degree">MD</roleName><affiliation>Institute of Brain Research, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Olaf</forename><surname>Riess</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</affiliation></author><author><persName><forename type="first">Abdelhaq</forename><surname>Rami</surname></persName><roleName type="degree">PhD</roleName><affiliation>Institute for Cellular and Molecular Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation></author><author><persName><forename type="first">Wilfried F. A.</forename><surname>Den Dunnen</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</affiliation></author><author><persName><forename type="first">Thomas</forename><surname>Deller</surname></persName><roleName type="degree">MD</roleName><affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation></author><author><persName><forename type="first">Udo</forename><surname>Rüb</surname></persName><roleName type="degree">MD</roleName><affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation><affiliation>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</affiliation></author><author><persName><forename type="first">Rejko</forename><surname>Krüger</surname></persName><roleName type="degree">MD</roleName><affiliation>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</affiliation><affiliation>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</affiliation></author></analytic><monogr><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="pISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><idno type="DOI">10.1002/(ISSN)1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-05"></date><biblScope unit="volume">67</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="684">684</biblScope><biblScope unit="page" to="689">689</biblScope></imprint></monogr><idno type="istex">7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B</idno><idno type="DOI">10.1002/ana.21966</idno><idno type="ArticleID">ANA21966</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha‐synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha‐synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha‐synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha‐synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. 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date="2014-10-14"></event></eventGroup><numberingGroup><numbering type="pageFirst">684</numbering><numbering type="pageLast">689</numbering></numberingGroup><correspondenceTo><lineatedText><line>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, Germany</line><line>Rejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</line></lineatedText></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:ANA.ANA21966.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="3"></count><count type="tableTotal" number="0"></count><count type="referenceTotal" number="21"></count><count type="wordTotal" number="3274"></count></countGroup><titleGroup><title type="main" xml:lang="en">First appraisal of brain pathology owing to A30P mutant alpha‐synuclein</title><title type="short" xml:lang="en">A30P Family Pathoanatomy</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Kay</givenNames><familyName>Seidel</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Ludger</givenNames><familyName>Schöls</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Silke</givenNames><familyName>Nuber</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af4"><personName><givenNames>Elisabeth</givenNames><familyName>Petrasch‐Parwez</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af5"><personName><givenNames>Kristin</givenNames><familyName>Gierga</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af6"><personName><givenNames>Zbigniew</givenNames><familyName>Wszolek</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af7"><personName><givenNames>Dennis</givenNames><familyName>Dickson</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au8" creatorRole="author" affiliationRef="#af8"><personName><givenNames>Wei P.</givenNames><familyName>Gai</familyName><degrees>PhD, MD</degrees></personName></creator><creator xml:id="au9" creatorRole="author" affiliationRef="#af9"><personName><givenNames>Antje</givenNames><familyName>Bornemann</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au10" creatorRole="author" 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A.</givenNames><familyName>Den Dunnen</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au13" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Thomas</givenNames><familyName>Deller</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au14" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Udo</givenNames><familyName>Rüb</familyName><degrees>MD</degrees></personName><contactDetails><email>Drueb@gmx.de</email></contactDetails></creator><creator xml:id="au15" creatorRole="author" affiliationRef="#af2" corresponding="yes"><personName><givenNames>Rejko</givenNames><familyName>Krüger</familyName><degrees>MD</degrees></personName><contactDetails><email normalForm="rejko.krueger@uni-tuebingen.de">rejko.krueger@uni‐tuebingen.de</email></contactDetails></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="DE" type="organization"><unparsedAffiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="DE" type="organization"><unparsedAffiliation>Neuroanatomy and Molecular Brain Research, Ruhr‐University Bochum, Bochum, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="DE" type="organization"><unparsedAffiliation>Department of Neuropathology, Heinrich‐Heine‐University, Düsseldorf, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, Mayo Clinic, Jacksonville, FL</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="US" type="organization"><unparsedAffiliation>Neuropathology Laboratory, Mayo Clinic, Jacksonville, FL</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="AU" type="organization"><unparsedAffiliation>Department of Human Physiology, Flinders University School of Medicine, Bedford Park, Australia</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="DE" type="organization"><unparsedAffiliation>Institute of Brain Research, University of Tübingen, Tübingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="DE" type="organization"><unparsedAffiliation>Institute for Cellular and Molecular Anatomy, Goethe University, Frankfurt am Main, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="NL" type="organization"><unparsedAffiliation>Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</unparsedAffiliation></affiliation></affiliationGroup><fundingInfo><fundingAgency>Deutsche Forschungsgemeinschaft</fundingAgency><fundingNumber>RU 1215/1‐2</fundingNumber><fundingNumber>KR2119/3‐1</fundingNumber></fundingInfo><fundingInfo><fundingAgency>Federal Ministry for Education and Research</fundingAgency><fundingNumber>01GS01834</fundingNumber></fundingInfo><supportingInformation><p> Additional Supporting Information may be found in the online version of this article. </p><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_SupplFigure1"></mediaResource><caption>Supplementary Figure 1: Predominantly neuronal alpha‐synuclein immunopositive inclusion bodies in the cerebral cortex, amygdala, hypothalamus, and thalamus (A) Allocortical entorhinal region: abundant alpha‐synuclein immunopositive LBs in the deep layers V and VI (arrows). (B) Allocortical hippocampus: Severe affection of the CA1, CA2, and CA3 sectors and slight affection of the fascia dentata (FD) by alpha‐synuclein immunopositive neuronal inclusions bodies. (C) Amygdala: Close‐meshed network of alpha‐synuclein immunopositive LBs and LNs in the central nucleus (CE) and markedly affected intercalated nucleus (IC). (D) Hypothalamus: Remarkable involvement of the tuberomammillary nucleus (TUM). (E) Dense mesh of alpha‐synuclein immunopositive LBs and LNs in the intralaminar central medial (CEM) and cucullar (CU) thalamic nuclei, as well as in the anterodorsal nucleus (AD) of the thalamus. Note the additional slight involvement of the thalamic anteroprincipal (AP) and mediodorsal nuclei (MD). (F) Severe affection of the thalamic intralaminar central medial (CEM) nucleus and the paraventricular nuclei (PV). (G) Selective vulnerability of the islands of the intralaminar central lateral nucleus (CL) of the thalamus intermingled among the nearly unaffected nerve cells of the medial subnucleus of the pulvinar (PU m). (H) Dense network of LBs and LNs in the limitans‐suprageniculate complex (LI‐SG) lying at the border between the thalamus and the midbrain. Note the marked involvement of the pretectum (PR). (A‐H: anti‐alpha‐synuclein immunocytochemistry, 100 μm PEG sections). Abbreviations: AD – Anterodorsal nucleus of the thalamus; AP – Anteroprincipal nucleus of the thalamus; CA1 – CA1 sector of the hippocampus; CA2 – CA2 sector of the hippocampus; CA3 – CA3 sector of the hippocampus; CE – Central nucleus of the amygdala; CEM – Central medial nucleus of the thalamus; CL – Central lateral nucleus of the thalamus; CU – Cucullar nucleus of the thalamus; FD – Fascia dentata; FO – Fornix; IC – Intercalate nucleus of the amygdala; LI‐SG – Limitans‐suprageniculate‐complex of the thalamus; MD – Mediodorsal nucleus of the thalamus; PR – Pretectum; PU m – Pulvinar, medial subnucleus; PV – Paraventricular nuclei of the thalamus; TUM – Tuberomammillary nucleus of the hypothalamus; IV – Cortical layer IV; V – Cortical layer V; VI – Cortical</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_SupplFigure2"></mediaResource><caption>Supplementary Figure 2: Alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in subthalamic and brainstem nuclei, as well as alpha‐synuclein immunopositive brainstem fiber tracts (A) Abundance of alpha‐synuclein immunopositive neuronal (arrow) and oligodendroglial inclusions in the zona incerta (ZI) and slightly affected subthalamic nucleus (SU) (arrow). (B) High prevalence of alpha‐synuclein immunopositive LBs (arrow), LNs, and coiled bodies in the substantia nigra (SN). Note the considerable affection of the red nucleus (RD). (C) Dense network of alpha‐synuclein immunopositive LBs and LNs in the precerebellar reticulotegmental nucleus of the pons (RTTG) and markedly affected oral subnucleus of the pontine reticular formation (PNO). (D) Large amounts of LBs and LNs in the raphe magnus (RMG) and gigantocellular reticular nuclei (GI). Additional LBs (arrow) are present in the dorsal accessory subnucleus of the inferior olive (IOD). (E) Severe affection of the dorsal motor vagal (DMV) and solitary nuclei (SOL), as well as alpha‐synuclein immunopositive vagal nerve (X). (F) Severe alpha‐synuclein immunopositive inclusion body pathology in the intermediate reticular zone (IRZ) and the precerebellar lateral reticular nucleus (LRT). Note the alpha‐synuclein immunopositive fibers of the dorsal spinocerebellar tract (arrows). Alpha‐synuclein immunopositive (G) vestibular nerve (VIII) and (H) olivocerebellar fibers (arrowheads). (A‐H: anti‐alpha‐synuclein immunocytochemistry, 100 μm PEG sections). Abbreviations: DMV – Dorsal motor vagal nucleus; ICP – Inferior cerebellar peduncle; IOD – Inferior olive, dorsal accessory subnucleus; IOP – Inferior olive, principal subnucleus; IRZ – Intermediate reticular zone; GI – Gigantocellular reticular nucleus; LRT – Lateral reticular nucleus; PNO – Pontine reticular formation, oral subnucleus; RD – Red nucleus; RMG – Raphe magnus nucleus; RTTG – Reticulotegmental nucleus of the pons; SN – Substantia Nigra; SOL – Solitary nuclei; SOL – Solitary tract; SU – Subthalamic nucleus; ZI – Zona incerta; VIII – Vestibular nerve; X – Vagal nerve</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_SupplFigure3"></mediaResource><caption>Supplementary Figure 3: No colocalization of alpha‐synuclein and tau pathologies in the dorsal raphe nucleus and intermediate reticular zone of the A30P patient Immunofluorescent images displaying concomitant (A) alpha‐synuclein and (B) tau inclusion pathologies in the intermediate reticular zone of the A30P patient, which (C) do not colocalize. (D) The alpha‐synuclein and (E) tau aggregates likewise (F) do not colocalize in the dorsal raphe nucleus of the A30P patient. (A‐F: Immunofluorescence staining of alpha‐synuclein inclusion pathology with alexa 568 chromogen (red) and tau inclusion pathology with alexa 488 (green), 100 μm PEG sections).</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_suppltext"></mediaResource><caption>Supplemental Material</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_Suppl_TABLE1"></mediaResource><caption>Table 1: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in the cerebral cortex, basal forebrain, basal ganglia and amygdala of the A30P index patient affected by both LBs and/or LNs and coiled bodies (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++).</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_Suppl_TABLE2"></mediaResource><caption>Table 2: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in the thalamus and hypothalamus of the A30P index patient affected by both LBs and/or LNs (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++).</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_Suppl_TABLE3"></mediaResource><caption>Table 3: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in subthalamic nuclei, the midbrain and pons of the A30P index patient affected by both LBs and/or LNs (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++).</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_Suppl_TABLE4"></mediaResource><caption>Table 4: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in the medulla oblongata and cerebellum of the A30P index patient affected by both LBs and/or LNs (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++).</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_Suppl_TABLE5"></mediaResource><caption>Table 5: Extent of alpha‐synuclein immunoreactive fibers in the central nervous white matter components of the A30P index patient showing additional oligodendroglial inclusions (IF, immunoreactive fibers; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++).</caption></supportingInfoItem><supportingInfoItem><mediaResource alt="supporting information" href="urn-x:wiley:03645134:media:ana21966:ANA_21966_sm_Suppl_TABLE6"></mediaResource><caption>Table 6: Clinical and pathological characteristics of brain donors used for biochemical studies.</caption></supportingInfoItem></supportingInformation><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>Familial Parkinson disease (PD) due to the A30P mutation in the <i>SNCA</i> gene encoding alpha‐synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha‐synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha‐synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha‐synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684–689</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>First appraisal of brain pathology owing to A30P mutant alpha‐synuclein</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>A30P Family Pathoanatomy</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>First appraisal of brain pathology owing to A30P mutant alpha‐synuclein</title></titleInfo><name type="personal"><namePart type="given">Kay</namePart><namePart type="family">Seidel</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ludger</namePart><namePart type="family">Schöls</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Silke</namePart><namePart type="family">Nuber</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elisabeth</namePart><namePart type="family">Petrasch‐Parwez</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neuroanatomy and Molecular Brain Research, Ruhr‐University Bochum, Bochum, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kristin</namePart><namePart type="family">Gierga</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neuropathology, Heinrich‐Heine‐University, Düsseldorf, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Zbigniew</namePart><namePart type="family">Wszolek</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, Mayo Clinic, Jacksonville, FL</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dennis</namePart><namePart type="family">Dickson</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Neuropathology Laboratory, Mayo Clinic, Jacksonville, FL</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wei P.</namePart><namePart type="family">Gai</namePart><namePart type="termsOfAddress">PhD, MD</namePart><affiliation>Department of Human Physiology, Flinders University School of Medicine, Bedford Park, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Antje</namePart><namePart type="family">Bornemann</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institute of Brain Research, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Olaf</namePart><namePart type="family">Riess</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Abdelhaq</namePart><namePart type="family">Rami</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>Institute for Cellular and Molecular Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Wilfried F. A.</namePart><namePart type="family">Den Dunnen</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Deller</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Udo</namePart><namePart type="family">Rüb</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Institute of Clinical Neuroanatomy, Dr Senckenberg Anatomy, Goethe University, Frankfurt am Main, Germany</affiliation><affiliation>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rejko</namePart><namePart type="family">Krüger</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Center of Neurology and Hertie‐Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany</affiliation><affiliation>Udo Rüb, Institute of Clinical Neuroanatomy, Dr. Senckenberg Anatomy, Goethe University, Theodor‐Stern‐Kai 7, D‐60590 Frankfurt/Main, GermanyRejko Krüger, Center of Neurology and Hertie‐Insitute for Clinical Brain Research, University of Tübingen, Hoppe‐Seyler‐Str. 3, 72076 Tübingen, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="brief communication" displayLabel="shortCommunication"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2010-05</dateIssued><dateCaptured encoding="w3cdtf">2009-06-30</dateCaptured><dateValid encoding="w3cdtf">2009-12-22</dateValid><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">3</extent><extent unit="references">21</extent><extent unit="words">3274</extent></physicalDescription><abstract lang="en">Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha‐synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha‐synuclein immunopositive Lewy bodies, Lewy neurites, and glial aggregates. Alpha‐synuclein aggregates ultrastructurally resembled Lewy bodies, and biochemical analyses disclosed a significant load of insoluble alpha‐synuclein, indicating neuropathological similarities between A30P disease patients and idiopathic PD, with a more severe neuropathology in A30P carriers. ANN NEUROL 2010;67:684–689</abstract><note type="funding">Deutsche Forschungsgemeinschaft - No. RU 1215/1‐2; No. KR2119/3‐1; </note><note type="funding">Federal Ministry for Education and Research - No. 01GS01834; </note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><note type="content"> Additional Supporting Information may be found in the online version of this article.Supporting Info Item: Supplementary Figure 1: Predominantly neuronal alpha‐synuclein immunopositive inclusion bodies in the cerebral cortex, amygdala, hypothalamus, and thalamus (A) Allocortical entorhinal region: abundant alpha‐synuclein immunopositive LBs in the deep layers V and VI (arrows). (B) Allocortical hippocampus: Severe affection of the CA1, CA2, and CA3 sectors and slight affection of the fascia dentata (FD) by alpha‐synuclein immunopositive neuronal inclusions bodies. (C) Amygdala: Close‐meshed network of alpha‐synuclein immunopositive LBs and LNs in the central nucleus (CE) and markedly affected intercalated nucleus (IC). (D) Hypothalamus: Remarkable involvement of the tuberomammillary nucleus (TUM). (E) Dense mesh of alpha‐synuclein immunopositive LBs and LNs in the intralaminar central medial (CEM) and cucullar (CU) thalamic nuclei, as well as in the anterodorsal nucleus (AD) of the thalamus. Note the additional slight involvement of the thalamic anteroprincipal (AP) and mediodorsal nuclei (MD). (F) Severe affection of the thalamic intralaminar central medial (CEM) nucleus and the paraventricular nuclei (PV). (G) Selective vulnerability of the islands of the intralaminar central lateral nucleus (CL) of the thalamus intermingled among the nearly unaffected nerve cells of the medial subnucleus of the pulvinar (PU m). (H) Dense network of LBs and LNs in the limitans‐suprageniculate complex (LI‐SG) lying at the border between the thalamus and the midbrain. Note the marked involvement of the pretectum (PR). (A‐H: anti‐alpha‐synuclein immunocytochemistry, 100 μm PEG sections). Abbreviations: AD – Anterodorsal nucleus of the thalamus; AP – Anteroprincipal nucleus of the thalamus; CA1 – CA1 sector of the hippocampus; CA2 – CA2 sector of the hippocampus; CA3 – CA3 sector of the hippocampus; CE – Central nucleus of the amygdala; CEM – Central medial nucleus of the thalamus; CL – Central lateral nucleus of the thalamus; CU – Cucullar nucleus of the thalamus; FD – Fascia dentata; FO – Fornix; IC – Intercalate nucleus of the amygdala; LI‐SG – Limitans‐suprageniculate‐complex of the thalamus; MD – Mediodorsal nucleus of the thalamus; PR – Pretectum; PU m – Pulvinar, medial subnucleus; PV – Paraventricular nuclei of the thalamus; TUM – Tuberomammillary nucleus of the hypothalamus; IV – Cortical layer IV; V – Cortical layer V; VI – Cortical - Supplementary Figure 2: Alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in subthalamic and brainstem nuclei, as well as alpha‐synuclein immunopositive brainstem fiber tracts (A) Abundance of alpha‐synuclein immunopositive neuronal (arrow) and oligodendroglial inclusions in the zona incerta (ZI) and slightly affected subthalamic nucleus (SU) (arrow). (B) High prevalence of alpha‐synuclein immunopositive LBs (arrow), LNs, and coiled bodies in the substantia nigra (SN). Note the considerable affection of the red nucleus (RD). (C) Dense network of alpha‐synuclein immunopositive LBs and LNs in the precerebellar reticulotegmental nucleus of the pons (RTTG) and markedly affected oral subnucleus of the pontine reticular formation (PNO). (D) Large amounts of LBs and LNs in the raphe magnus (RMG) and gigantocellular reticular nuclei (GI). Additional LBs (arrow) are present in the dorsal accessory subnucleus of the inferior olive (IOD). (E) Severe affection of the dorsal motor vagal (DMV) and solitary nuclei (SOL), as well as alpha‐synuclein immunopositive vagal nerve (X). (F) Severe alpha‐synuclein immunopositive inclusion body pathology in the intermediate reticular zone (IRZ) and the precerebellar lateral reticular nucleus (LRT). Note the alpha‐synuclein immunopositive fibers of the dorsal spinocerebellar tract (arrows). Alpha‐synuclein immunopositive (G) vestibular nerve (VIII) and (H) olivocerebellar fibers (arrowheads). (A‐H: anti‐alpha‐synuclein immunocytochemistry, 100 μm PEG sections). Abbreviations: DMV – Dorsal motor vagal nucleus; ICP – Inferior cerebellar peduncle; IOD – Inferior olive, dorsal accessory subnucleus; IOP – Inferior olive, principal subnucleus; IRZ – Intermediate reticular zone; GI – Gigantocellular reticular nucleus; LRT – Lateral reticular nucleus; PNO – Pontine reticular formation, oral subnucleus; RD – Red nucleus; RMG – Raphe magnus nucleus; RTTG – Reticulotegmental nucleus of the pons; SN – Substantia Nigra; SOL – Solitary nuclei; SOL – Solitary tract; SU – Subthalamic nucleus; ZI – Zona incerta; VIII – Vestibular nerve; X – Vagal nerve - Supplementary Figure 3: No colocalization of alpha‐synuclein and tau pathologies in the dorsal raphe nucleus and intermediate reticular zone of the A30P patient Immunofluorescent images displaying concomitant (A) alpha‐synuclein and (B) tau inclusion pathologies in the intermediate reticular zone of the A30P patient, which (C) do not colocalize. (D) The alpha‐synuclein and (E) tau aggregates likewise (F) do not colocalize in the dorsal raphe nucleus of the A30P patient. (A‐F: Immunofluorescence staining of alpha‐synuclein inclusion pathology with alexa 568 chromogen (red) and tau inclusion pathology with alexa 488 (green), 100 μm PEG sections). - Supplemental Material - Table 1: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in the cerebral cortex, basal forebrain, basal ganglia and amygdala of the A30P index patient affected by both LBs and/or LNs and coiled bodies (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++). - Table 2: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in the thalamus and hypothalamus of the A30P index patient affected by both LBs and/or LNs (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++). - Table 3: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in subthalamic nuclei, the midbrain and pons of the A30P index patient affected by both LBs and/or LNs (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++). - Table 4: Distribution and extent of alpha‐synuclein immunopositive neuronal and oligodendroglial inclusions in the medulla oblongata and cerebellum of the A30P index patient affected by both LBs and/or LNs (L, Lewy bodies and/or Lewy neurites; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++). - Table 5: Extent of alpha‐synuclein immunoreactive fibers in the central nervous white matter components of the A30P index patient showing additional oligodendroglial inclusions (IF, immunoreactive fibers; C, coiled bodies; not discernible 0, mild +, marked ++, severe +++). - Table 6: Clinical and pathological characteristics of brain donors used for biochemical studies. - </note><subject><genre>article category</genre><topic>Brief Communication</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>67</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>684</start><end>689</end><total>6</total></extent></part></relatedItem><identifier type="istex">7C1C7B5D85249FE37FBA90B434AF6A9FD9432A9B</identifier><identifier type="DOI">10.1002/ana.21966</identifier><identifier type="ArticleID">ANA21966</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2010 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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