Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43
Identifieur interne : 002756 ( Main/Corpus ); précédent : 002755; suivant : 002757Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43
Auteurs : Andrew King ; Satomi Maekawa ; Istvan Bodi ; Claire Troakes ; Safa Al-SarrajSource :
- Neuropathology [ 0919-6544 ] ; 2011-06.
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Abstract
Frontotemporal lobar degeneration with TDP‐43‐positive inclusions (FTLD‐TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD‐MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP‐43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP‐43 proteinopathies (including cases of FTLD‐TDP, FTLD‐MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP‐43 proteinopathies (26%) there were numerous p62‐positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation‐independent TDP‐43, hyperphosphorylated tau, α‐synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD‐TDP) were the inclusions positive for phosphorylation‐dependent TDP43 (p‐TDP‐43). Those TDP‐43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP‐43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62‐positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP‐43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar‐positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.
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DOI: 10.1111/j.1440-1789.2010.01171.x
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Bodi</name><affiliation><mods:affiliation>Department of Clinical Neuropathology, King's College Hospital, and</mods:affiliation></affiliation></author><author><name sortKey="Troakes, Claire" sort="Troakes, Claire" uniqKey="Troakes C" first="Claire" last="Troakes">Claire Troakes</name><affiliation><mods:affiliation>MRC Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, King's College, London, UK</mods:affiliation></affiliation></author><author><name sortKey="Al Arraj, Safa" sort="Al Arraj, Safa" uniqKey="Al Arraj S" first="Safa" last="Al-Sarraj">Safa Al-Sarraj</name><affiliation><mods:affiliation>Department of Clinical Neuropathology, King's College Hospital, and</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1D04BE87D8F4732BEACA1AB92234A204998B9D07</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1111/j.1440-1789.2010.01171.x</idno><idno 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and</mods:affiliation></affiliation></author><author><name sortKey="Bodi, Istvan" sort="Bodi, Istvan" uniqKey="Bodi I" first="Istvan" last="Bodi">Istvan Bodi</name><affiliation><mods:affiliation>Department of Clinical Neuropathology, King's College Hospital, and</mods:affiliation></affiliation></author><author><name sortKey="Troakes, Claire" sort="Troakes, Claire" uniqKey="Troakes C" first="Claire" last="Troakes">Claire Troakes</name><affiliation><mods:affiliation>MRC Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, King's College, London, UK</mods:affiliation></affiliation></author><author><name sortKey="Al Arraj, Safa" sort="Al Arraj, Safa" uniqKey="Al Arraj S" first="Safa" last="Al-Sarraj">Safa Al-Sarraj</name><affiliation><mods:affiliation>Department of Clinical Neuropathology, King's College Hospital, and</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Neuropathology</title><idno type="ISSN">0919-6544</idno><idno 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degeneration with TDP‐43‐positive inclusions (FTLD‐TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD‐MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP‐43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP‐43 proteinopathies (including cases of FTLD‐TDP, FTLD‐MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP‐43 proteinopathies (26%) there were numerous p62‐positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation‐independent TDP‐43, hyperphosphorylated tau, α‐synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD‐TDP) were the inclusions positive for phosphorylation‐dependent TDP43 (p‐TDP‐43). Those TDP‐43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP‐43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62‐positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP‐43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar‐positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Andrew King</name><affiliations><json:string>Department of Clinical Neuropathology, King's College Hospital, and</json:string></affiliations></json:item><json:item><name>Satomi Maekawa</name><affiliations><json:string>Department of Clinical Neuropathology, King's College Hospital, and</json:string></affiliations></json:item><json:item><name>Istvan Bodi</name><affiliations><json:string>Department of Clinical Neuropathology, King's College Hospital, and</json:string></affiliations></json:item><json:item><name>Claire Troakes</name><affiliations><json:string>MRC Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, King's College, London, UK</json:string></affiliations></json:item><json:item><name>Safa Al‐Sarraj</name><affiliations><json:string>Department of Clinical Neuropathology, King's College Hospital, and</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>cerebellum</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dementia</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>p62</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>proteinopathy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>TDP‐43</value></json:item></subject><articleId><json:string>NEUP1171</json:string></articleId><language><json:string>eng</json:string></language><abstract>Frontotemporal lobar degeneration with TDP‐43‐positive inclusions (FTLD‐TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD‐MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP‐43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP‐43 proteinopathies (including cases of FTLD‐TDP, FTLD‐MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP‐43 proteinopathies (26%) there were numerous p62‐positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation‐independent TDP‐43, hyperphosphorylated tau, α‐synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD‐TDP) were the inclusions positive for phosphorylation‐dependent TDP43 (p‐TDP‐43). Those TDP‐43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP‐43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62‐positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP‐43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar‐positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.</abstract><qualityIndicators><score>8</score><pdfVersion>1.3</pdfVersion><pdfPageSize>595.276 x 810.709 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>2088</abstractCharCount><pdfWordCount>5854</pdfWordCount><pdfCharCount>40298</pdfCharCount><pdfPageCount>11</pdfPageCount><abstractWordCount>281</abstractWordCount></qualityIndicators><title>Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43</title><genre><json:string>article</json:string></genre><host><volume>31</volume><publisherId><json:string>NEUP</json:string></publisherId><pages><total>11</total><last>249</last><first>239</first></pages><issn><json:string>0919-6544</json:string></issn><issue>3</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><eissn><json:string>1440-1789</json:string></eissn><title>Neuropathology</title><doi><json:string>10.1111/(ISSN)1440-1789</json:string></doi></host><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1111/j.1440-1789.2010.01171.x</json:string></doi><id>1D04BE87D8F4732BEACA1AB92234A204998B9D07</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/1D04BE87D8F4732BEACA1AB92234A204998B9D07/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/1D04BE87D8F4732BEACA1AB92234A204998B9D07/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/1D04BE87D8F4732BEACA1AB92234A204998B9D07/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Asia</publisher><pubPlace>Melbourne, Australia</pubPlace><availability><p>WILEY</p></availability><date>2011</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43</title><author><persName><forename type="first">Andrew</forename><surname>King</surname></persName><note type="correspondence"><p>Correspondence: Andrew King, FRCPath, Department of Clinical Neuropathology, Academic Neuroscience Building, King's College Hospital, Denmark Hill, London SE5 9RS, UK. Email:</p></note><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation></author><author><persName><forename type="first">Satomi</forename><surname>Maekawa</surname></persName><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation></author><author><persName><forename type="first">Istvan</forename><surname>Bodi</surname></persName><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation></author><author><persName><forename type="first">Claire</forename><surname>Troakes</surname></persName><affiliation>MRC Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, King's College, London, UK</affiliation></author><author><persName><forename type="first">Safa</forename><surname>Al‐Sarraj</surname></persName><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation></author></analytic><monogr><title level="j">Neuropathology</title><idno type="pISSN">0919-6544</idno><idno type="eISSN">1440-1789</idno><idno type="DOI">10.1111/(ISSN)1440-1789</idno><imprint><publisher>Blackwell Publishing Asia</publisher><pubPlace>Melbourne, Australia</pubPlace><date type="published" when="2011-06"></date><biblScope unit="volume">31</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="239">239</biblScope><biblScope unit="page" to="249">249</biblScope></imprint></monogr><idno type="istex">1D04BE87D8F4732BEACA1AB92234A204998B9D07</idno><idno type="DOI">10.1111/j.1440-1789.2010.01171.x</idno><idno type="ArticleID">NEUP1171</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Frontotemporal lobar degeneration with TDP‐43‐positive inclusions (FTLD‐TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD‐MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP‐43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP‐43 proteinopathies (including cases of FTLD‐TDP, FTLD‐MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP‐43 proteinopathies (26%) there were numerous p62‐positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation‐independent TDP‐43, hyperphosphorylated tau, α‐synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD‐TDP) were the inclusions positive for phosphorylation‐dependent TDP43 (p‐TDP‐43). Those TDP‐43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP‐43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62‐positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP‐43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar‐positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>cerebellum</term></item><item><term>dementia</term></item><item><term>p62</term></item><item><term>proteinopathy</term></item><item><term>TDP‐43</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-06">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/1D04BE87D8F4732BEACA1AB92234A204998B9D07/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Blackwell Publishing Asia</publisherName><publisherLoc>Melbourne, Australia</publisherLoc></publisherInfo><doi origin="wiley" registered="yes">10.1111/(ISSN)1440-1789</doi><issn type="print">0919-6544</issn><issn type="electronic">1440-1789</issn><idGroup><id type="product" value="NEUP"></id><id type="publisherDivision" value="ST"></id></idGroup><titleGroup><title type="main" sort="NEUROPATHOLOGY">Neuropathology</title></titleGroup></publicationMeta><publicationMeta level="part" position="06103"><doi origin="wiley">10.1111/neu.2011.31.issue-3</doi><numberingGroup><numbering type="journalVolume" number="31">31</numbering><numbering type="journalIssue" number="3">3</numbering></numberingGroup><coverDate startDate="2011-06">June 2011</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="6" status="forIssue"><doi origin="wiley">10.1111/j.1440-1789.2010.01171.x</doi><idGroup><id type="unit" value="NEUP1171"></id></idGroup><countGroup><count type="pageTotal" number="11"></count></countGroup><titleGroup><title type="tocHeading1">ORIGINAL ARTICLES</title></titleGroup><copyright>© 2010 Japanese Society of Neuropathology</copyright><eventGroup><event type="xmlConverted" agent="Converter:BPG_TO_WML3G version:2.4.9 mode:FullText" date="2011-05-26"></event><event type="publishedOnlineEarlyUnpaginated" date="2010-12-01"></event><event type="firstOnline" date="2010-12-01"></event><event type="publishedOnlineFinalForm" date="2011-05-26"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-03"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.1.7 mode:FullText,remove_FC" date="2014-11-01"></event></eventGroup><numberingGroup><numbering type="pageFirst" number="239">239</numbering><numbering type="pageLast" number="249">249</numbering></numberingGroup><correspondenceTo>Andrew King, FRCPath, Department of Clinical Neuropathology, Academic Neuroscience Building, King's College Hospital, Denmark Hill, London SE5 9RS, UK. Email: <email>andrewking@nhs.net</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:NEUP.NEUP1171.pdf"></link></linkGroup></publicationMeta><contentMeta><unparsedEditorialHistory>Received 26 May 2010; revised 3 September 2010 and accepted 20 September 2010; published online 1 December 2010.</unparsedEditorialHistory><countGroup><count type="figureTotal" number="2"></count><count type="tableTotal" number="3"></count><count type="formulaTotal" number="0"></count><count type="referenceTotal" number="43"></count><count type="wordTotal" number="7170"></count><count type="linksPubMed" number="0"></count><count type="linksCrossRef" number="0"></count></countGroup><titleGroup><title type="main">Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43</title><title type="shortAuthors">A King <i>et al.</i></title><title type="short">Cerebellar p62 in TDP‐43‐opathies</title></titleGroup><creators><creator creatorRole="author" xml:id="cr1" affiliationRef="#a1" corresponding="yes"><personName><givenNames>Andrew</givenNames><familyName>King</familyName></personName></creator><creator creatorRole="author" xml:id="cr2" affiliationRef="#a1"><personName><givenNames>Satomi</givenNames><familyName>Maekawa</familyName></personName></creator><creator creatorRole="author" xml:id="cr3" affiliationRef="#a1"><personName><givenNames>Istvan</givenNames><familyName>Bodi</familyName></personName></creator><creator creatorRole="author" xml:id="cr4" affiliationRef="#a2"><personName><givenNames>Claire</givenNames><familyName>Troakes</familyName></personName></creator><creator creatorRole="author" xml:id="cr5" affiliationRef="#a1"><personName><givenNames>Safa</givenNames><familyName>Al‐Sarraj</familyName></personName></creator></creators><affiliationGroup><affiliation xml:id="a1"><unparsedAffiliation>Department of Clinical Neuropathology, King's College Hospital, and</unparsedAffiliation></affiliation><affiliation xml:id="a2" countryCode="GB"><unparsedAffiliation>MRC Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, King's College, London, UK</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en"><keyword xml:id="k1">cerebellum</keyword><keyword xml:id="k2">dementia</keyword><keyword xml:id="k3">p62</keyword><keyword xml:id="k4">proteinopathy</keyword><keyword xml:id="k5">TDP‐43</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><p>Frontotemporal lobar degeneration with TDP‐43‐positive inclusions (FTLD‐TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD‐MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP‐43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP‐43 proteinopathies (including cases of FTLD‐TDP, FTLD‐MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP‐43 proteinopathies (26%) there were numerous p62‐positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation‐independent TDP‐43, hyperphosphorylated tau, α‐synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD‐TDP) were the inclusions positive for phosphorylation‐dependent TDP43 (p‐TDP‐43). Those TDP‐43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP‐43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62‐positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP‐43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar‐positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43</title></titleInfo><titleInfo type="abbreviated"><title>Cerebellar p62 in TDP‐43‐opathies</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Ubiquitinated, p62 immunopositive cerebellar cortical neuronal inclusions are evident across the spectrum of TDP‐43 proteinopathies but are only rarely additionally immunopositive for phosphorylation‐dependent TDP‐43</title></titleInfo><name type="personal"><namePart type="given">Andrew</namePart><namePart type="family">King</namePart><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation><description>Correspondence: Andrew King, FRCPath, Department of Clinical Neuropathology, Academic Neuroscience Building, King's College Hospital, Denmark Hill, London SE5 9RS, UK. Email: </description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Satomi</namePart><namePart type="family">Maekawa</namePart><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Istvan</namePart><namePart type="family">Bodi</namePart><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Claire</namePart><namePart type="family">Troakes</namePart><affiliation>MRC Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, King's College, London, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Safa</namePart><namePart type="family">Al‐Sarraj</namePart><affiliation>Department of Clinical Neuropathology, King's College Hospital, and</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Blackwell Publishing Asia</publisher><place><placeTerm type="text">Melbourne, Australia</placeTerm></place><dateIssued encoding="w3cdtf">2011-06</dateIssued><edition>Received 26 May 2010; revised 3 September 2010 and accepted 20 September 2010; published online 1 December 2010.</edition><copyrightDate encoding="w3cdtf">2011</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">2</extent><extent unit="tables">3</extent><extent unit="references">43</extent><extent unit="words">7170</extent></physicalDescription><abstract lang="en">Frontotemporal lobar degeneration with TDP‐43‐positive inclusions (FTLD‐TDP), frontotemporal lobar degeneration with motor neuron disease/amyotrophic lateral sclerosis (FTLD‐MND/ALS) and MND/ALS are thought to represent a clinicopathological spectrum of TDP‐43 proteinopathies. The cerebellum has been little studied in these conditions, probably because of the lack of cerebellar signs in most cases. We examined p62 immunohistochemistry on cerebellar sections from 43 TDP‐43 proteinopathies (including cases of FTLD‐TDP, FTLD‐MND/ALS and MND/ALS) together with 72 cases of other neurodegenerative diseases, seven controls and three other disease conditions. In 11 of the TDP‐43 proteinopathies (26%) there were numerous p62‐positive cerebellar inclusions, predominantly within the granular layer, but also the molecular and Purkinje cell layer. Furthermore, only one of the remaining 82 cases (a familial tauopathy) showed similar p62 positivity. Immunohistochemistry for ubiquitin was positive in the granular layer inclusions. The immunohistochemistry for phosphorylation‐independent TDP‐43, hyperphosphorylated tau, α‐synuclein, fusion sarcoma protein (FUS), and neurofilament was negative. In only one case (a case of FTLD‐TDP) were the inclusions positive for phosphorylation‐dependent TDP43 (p‐TDP‐43). Those TDP‐43 proteinopathy cases that showed the cerebellar inclusions also tended to display other common features, such as a notable excess of p62 pathology when compared to TDP‐43 pathology, especially within the pyramidal neurones of the hippocampus but also in some cases within the neocortex. The results suggest that p62‐positive inclusions within the cerebellum are seen in a proportion of cases across the range of the TDP‐43 proteinopathy spectrum and they appear to be relatively specific for this group of diseases. The question as to whether these cerebellar‐positive cases represent a distinct subgroup remains to be answered. Furthermore, the relationship of the p62 positivity in the cerebellum to the underlying pathological processes awaits to be established.</abstract><subject lang="en"><genre>Keywords</genre><topic>cerebellum</topic><topic>dementia</topic><topic>p62</topic><topic>proteinopathy</topic><topic>TDP‐43</topic></subject><relatedItem type="host"><titleInfo><title>Neuropathology</title></titleInfo><genre type="Journal">journal</genre><identifier type="ISSN">0919-6544</identifier><identifier type="eISSN">1440-1789</identifier><identifier type="DOI">10.1111/(ISSN)1440-1789</identifier><identifier type="PublisherID">NEUP</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>31</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>239</start><end>249</end><total>11</total></extent></part></relatedItem><identifier type="istex">1D04BE87D8F4732BEACA1AB92234A204998B9D07</identifier><identifier type="DOI">10.1111/j.1440-1789.2010.01171.x</identifier><identifier type="ArticleID">NEUP1171</identifier><accessCondition type="use and reproduction" contentType="copyright">© 2010 Japanese Society of Neuropathology</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Blackwell Publishing Asia</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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