Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons.
Identifieur interne : 001070 ( Main/Exploration ); précédent : 001069; suivant : 001071Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons.
Auteurs : S D Ginsberg [États-Unis] ; S E Hemby ; V M Lee ; J H Eberwine ; J Q TrojanowskiSource :
- Annals of neurology [ 0364-5134 ] ; 2000.
Descripteurs français
- KwdFr :
- ADN complémentaire (analyse), ARN antisens (analyse), ARN messager (analyse), Enchevêtrements neurofibrillaires (anatomopathologie), Enchevêtrements neurofibrillaires (génétique), Femelle (MeSH), Hippocampe (anatomopathologie), Humains (MeSH), Hybridation in situ (MeSH), Maladie d'Alzheimer (anatomopathologie), Maladie d'Alzheimer (génétique), Mâle (MeSH), Sujet âgé (MeSH), Transcription génétique (MeSH).
- MESH :
- analyse : ADN complémentaire, ARN antisens, ARN messager.
- anatomopathologie : Enchevêtrements neurofibrillaires, Hippocampe, Maladie d'Alzheimer.
- génétique : Enchevêtrements neurofibrillaires, Maladie d'Alzheimer.
- Femelle, Humains, Hybridation in situ, Mâle, Sujet âgé, Transcription génétique.
English descriptors
- KwdEn :
- Aged (MeSH), Alzheimer Disease (genetics), Alzheimer Disease (pathology), DNA, Complementary (analysis), Female (MeSH), Hippocampus (pathology), Humans (MeSH), In Situ Hybridization (MeSH), Male (MeSH), Neurofibrillary Tangles (genetics), Neurofibrillary Tangles (pathology), RNA, Antisense (analysis), RNA, Messenger (analysis), Transcription, Genetic (MeSH).
- MESH :
- chemical , analysis : DNA, Complementary, RNA, Antisense, RNA, Messenger.
- genetics : Alzheimer Disease, Neurofibrillary Tangles.
- pathology : Alzheimer Disease, Hippocampus, Neurofibrillary Tangles.
- Aged, Female, Humans, In Situ Hybridization, Male, Transcription, Genetic.
Abstract
The pathogenesis of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) is poorly understood, but changes in the expression of specific messenger RNAs (mRNAs) may reflect mechanisms underlying the formation of NFTs and their consequences in affected neurons. For these reasons, we compared the relative abundance of multiple mRNAs in tangle-bearing versus normal CA1 neurons aspirated from sections of AD and control brains. Amplified antisense RNA expression profiling was performed on individual isolated neurons for analysis of greater than 18,000 expressed sequence tagged complementary DNAs (cDNAs) with cDNA microarrays, and further quantitative analyses were performed by reverse Northern blot analysis on 120 selected mRNAs on custom cDNA arrays. Relative to normal CA1 neurons, those harboring NFTs in AD brains showed significant reductions in several classes of mRNAs that are known to encode proteins implicated in AD neuropathology, including phosphatases/kinases, cytoskeletal proteins, synaptic proteins, glutamate receptors, and dopamine receptors. Because cathepsin D mRNA was upregulated in NFT-bearing CA1 neurons in AD brains, we performed immunohistochemical studies that demonstrated abundant cathepsin D immunoreactivity in the same population of tangle-bearing CA1 neurons. In addition, levels of mRNAs encoding proteins not previously implicated in AD were reduced in CA1 tangle-bearing neurons, suggesting that these proteins (eg, activity-regulated cytoskeleton-associated protein, focal adhesion kinase, glutaredoxin, utrophin) may be novel mediators of NFT formation or degeneration in affected neurons. Thus, the profile of mRNAs differentially expressed by tangle-bearing CA1 neurons may represent a "molecular fingerprint" of these neurons, and we speculate that mRNA expression profiles of diseased neurons in AD may suggest new directions for AD research or identify novel targets for developing more effective AD therapies.
PubMed: 10894219
Affiliations:
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last="Hemby">S E Hemby</name></author><author><name sortKey="Lee, V M" sort="Lee, V M" uniqKey="Lee V" first="V M" last="Lee">V M Lee</name></author><author><name sortKey="Eberwine, J H" sort="Eberwine, J H" uniqKey="Eberwine J" first="J H" last="Eberwine">J H Eberwine</name></author><author><name sortKey="Trojanowski, J Q" sort="Trojanowski, J Q" uniqKey="Trojanowski J" first="J Q" last="Trojanowski">J Q Trojanowski</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:10894219</idno><idno type="pmid">10894219</idno><idno type="wicri:Area/Main/Corpus">001066</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001066</idno><idno type="wicri:Area/Main/Curation">001066</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001066</idno><idno type="wicri:Area/Main/Exploration">001066</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons.</title><author><name sortKey="Ginsberg, S D" sort="Ginsberg, S D" uniqKey="Ginsberg S" first="S D" last="Ginsberg">S D Ginsberg</name><affiliation wicri:level="1"><nlm:affiliation>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283</wicri:regionArea><placeName><settlement type="city">Philadelphie</settlement><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Hemby, S E" sort="Hemby, S E" uniqKey="Hemby S" first="S E" last="Hemby">S E Hemby</name></author><author><name sortKey="Lee, V M" sort="Lee, V M" uniqKey="Lee V" first="V M" last="Lee">V M Lee</name></author><author><name sortKey="Eberwine, J H" sort="Eberwine, J H" uniqKey="Eberwine J" first="J H" last="Eberwine">J H Eberwine</name></author><author><name sortKey="Trojanowski, J Q" sort="Trojanowski, J Q" uniqKey="Trojanowski J" first="J Q" last="Trojanowski">J Q Trojanowski</name></author></analytic><series><title level="j">Annals of neurology</title><idno type="ISSN">0364-5134</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Alzheimer Disease (genetics)</term><term>Alzheimer Disease (pathology)</term><term>DNA, Complementary (analysis)</term><term>Female (MeSH)</term><term>Hippocampus (pathology)</term><term>Humans (MeSH)</term><term>In Situ Hybridization (MeSH)</term><term>Male (MeSH)</term><term>Neurofibrillary Tangles (genetics)</term><term>Neurofibrillary Tangles (pathology)</term><term>RNA, Antisense (analysis)</term><term>RNA, Messenger (analysis)</term><term>Transcription, Genetic (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN complémentaire (analyse)</term><term>ARN antisens (analyse)</term><term>ARN messager (analyse)</term><term>Enchevêtrements neurofibrillaires (anatomopathologie)</term><term>Enchevêtrements neurofibrillaires (génétique)</term><term>Femelle (MeSH)</term><term>Hippocampe (anatomopathologie)</term><term>Humains (MeSH)</term><term>Hybridation in situ (MeSH)</term><term>Maladie d'Alzheimer (anatomopathologie)</term><term>Maladie d'Alzheimer (génétique)</term><term>Mâle (MeSH)</term><term>Sujet âgé (MeSH)</term><term>Transcription génétique (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>DNA, Complementary</term><term>RNA, Antisense</term><term>RNA, Messenger</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ADN complémentaire</term><term>ARN antisens</term><term>ARN messager</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Enchevêtrements neurofibrillaires</term><term>Hippocampe</term><term>Maladie d'Alzheimer</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Alzheimer Disease</term><term>Neurofibrillary Tangles</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Enchevêtrements neurofibrillaires</term><term>Maladie d'Alzheimer</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Alzheimer Disease</term><term>Hippocampus</term><term>Neurofibrillary Tangles</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Humans</term><term>In Situ Hybridization</term><term>Male</term><term>Transcription, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Femelle</term><term>Humains</term><term>Hybridation in situ</term><term>Mâle</term><term>Sujet âgé</term><term>Transcription génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The pathogenesis of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) is poorly understood, but changes in the expression of specific messenger RNAs (mRNAs) may reflect mechanisms underlying the formation of NFTs and their consequences in affected neurons. For these reasons, we compared the relative abundance of multiple mRNAs in tangle-bearing versus normal CA1 neurons aspirated from sections of AD and control brains. Amplified antisense RNA expression profiling was performed on individual isolated neurons for analysis of greater than 18,000 expressed sequence tagged complementary DNAs (cDNAs) with cDNA microarrays, and further quantitative analyses were performed by reverse Northern blot analysis on 120 selected mRNAs on custom cDNA arrays. Relative to normal CA1 neurons, those harboring NFTs in AD brains showed significant reductions in several classes of mRNAs that are known to encode proteins implicated in AD neuropathology, including phosphatases/kinases, cytoskeletal proteins, synaptic proteins, glutamate receptors, and dopamine receptors. Because cathepsin D mRNA was upregulated in NFT-bearing CA1 neurons in AD brains, we performed immunohistochemical studies that demonstrated abundant cathepsin D immunoreactivity in the same population of tangle-bearing CA1 neurons. In addition, levels of mRNAs encoding proteins not previously implicated in AD were reduced in CA1 tangle-bearing neurons, suggesting that these proteins (eg, activity-regulated cytoskeleton-associated protein, focal adhesion kinase, glutaredoxin, utrophin) may be novel mediators of NFT formation or degeneration in affected neurons. Thus, the profile of mRNAs differentially expressed by tangle-bearing CA1 neurons may represent a "molecular fingerprint" of these neurons, and we speculate that mRNA expression profiles of diseased neurons in AD may suggest new directions for AD research or identify novel targets for developing more effective AD therapies.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">10894219</PMID><DateCompleted><Year>2000</Year><Month>07</Month><Day>31</Day></DateCompleted><DateRevised><Year>2006</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0364-5134</ISSN><JournalIssue CitedMedium="Print"><Volume>48</Volume><Issue>1</Issue><PubDate><Year>2000</Year><Month>Jul</Month></PubDate></JournalIssue><Title>Annals of neurology</Title><ISOAbbreviation>Ann Neurol</ISOAbbreviation></Journal><ArticleTitle>Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons.</ArticleTitle><Pagination><MedlinePgn>77-87</MedlinePgn></Pagination><Abstract><AbstractText>The pathogenesis of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) is poorly understood, but changes in the expression of specific messenger RNAs (mRNAs) may reflect mechanisms underlying the formation of NFTs and their consequences in affected neurons. For these reasons, we compared the relative abundance of multiple mRNAs in tangle-bearing versus normal CA1 neurons aspirated from sections of AD and control brains. Amplified antisense RNA expression profiling was performed on individual isolated neurons for analysis of greater than 18,000 expressed sequence tagged complementary DNAs (cDNAs) with cDNA microarrays, and further quantitative analyses were performed by reverse Northern blot analysis on 120 selected mRNAs on custom cDNA arrays. Relative to normal CA1 neurons, those harboring NFTs in AD brains showed significant reductions in several classes of mRNAs that are known to encode proteins implicated in AD neuropathology, including phosphatases/kinases, cytoskeletal proteins, synaptic proteins, glutamate receptors, and dopamine receptors. Because cathepsin D mRNA was upregulated in NFT-bearing CA1 neurons in AD brains, we performed immunohistochemical studies that demonstrated abundant cathepsin D immunoreactivity in the same population of tangle-bearing CA1 neurons. In addition, levels of mRNAs encoding proteins not previously implicated in AD were reduced in CA1 tangle-bearing neurons, suggesting that these proteins (eg, activity-regulated cytoskeleton-associated protein, focal adhesion kinase, glutaredoxin, utrophin) may be novel mediators of NFT formation or degeneration in affected neurons. Thus, the profile of mRNAs differentially expressed by tangle-bearing CA1 neurons may represent a "molecular fingerprint" of these neurons, and we speculate that mRNA expression profiles of diseased neurons in AD may suggest new directions for AD research or identify novel targets for developing more effective AD therapies.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ginsberg</LastName><ForeName>S D</ForeName><Initials>SD</Initials><AffiliationInfo><Affiliation>Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hemby</LastName><ForeName>S E</ForeName><Initials>SE</Initials></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>V M</ForeName><Initials>VM</Initials></Author><Author ValidYN="Y"><LastName>Eberwine</LastName><ForeName>J H</ForeName><Initials>JH</Initials></Author><Author ValidYN="Y"><LastName>Trojanowski</LastName><ForeName>J Q</ForeName><Initials>JQ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Ann Neurol</MedlineTA><NlmUniqueID>7707449</NlmUniqueID><ISSNLinking>0364-5134</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018076">DNA, Complementary</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016372">RNA, Antisense</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000544" MajorTopicYN="N">Alzheimer Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018076" MajorTopicYN="N">DNA, Complementary</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006624" MajorTopicYN="N">Hippocampus</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017403" MajorTopicYN="N">In Situ Hybridization</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016874" MajorTopicYN="N">Neurofibrillary Tangles</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016372" MajorTopicYN="N">RNA, Antisense</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName><QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014158" MajorTopicYN="N">Transcription, Genetic</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>7</Month><Day>14</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2000</Year><Month>8</Month><Day>6</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>7</Month><Day>14</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10894219</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Philadelphie</li></settlement></list><tree><noCountry><name sortKey="Eberwine, J H" sort="Eberwine, J H" uniqKey="Eberwine J" first="J H" last="Eberwine">J H Eberwine</name><name sortKey="Hemby, S E" sort="Hemby, S E" uniqKey="Hemby S" first="S E" last="Hemby">S E Hemby</name><name sortKey="Lee, V M" sort="Lee, V M" uniqKey="Lee V" first="V M" last="Lee">V M Lee</name><name sortKey="Trojanowski, J Q" sort="Trojanowski, J Q" uniqKey="Trojanowski J" first="J Q" last="Trojanowski">J Q Trojanowski</name></noCountry><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Ginsberg, S D" sort="Ginsberg, S D" uniqKey="Ginsberg S" first="S D" last="Ginsberg">S D Ginsberg</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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