Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders
Identifieur interne : 001704 ( Main/Corpus ); précédent : 001703; suivant : 001705Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders
Auteurs : Peter K. Panegyres ; K. Zafiris-Toufexis ; B. A. KakulasSource :
- Journal of the Neurological Sciences [ 0022-510X ] ; 1999.
Abstract
Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer’s disease (AD) and experimentally in the brain’s response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI−). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with 35S to detect the two principal splice variants of APP: APP 695 (KPI−) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (n=15) and other neurodegenerative disorders as controls (n=18). The controls consist of frontal lobe atrophy (n=4), Huntington’s disease (n=5), Parkinson’s disease (n=4), motor neuron disease (n=2), multi-infarct dementia (n=1), multisystem atrophy (n=1), and subacute sclerosing panencephalitis (n=1). We have observed no significant differences in the expression of APP 695 KPI– mRNA in frontal lobe: 17.49±3.26 optical density (OD) units of mRNA expression in AD vs. 16.13±1.76 OD units mRNA in controls (P=0.80, linear regression); or temporal lobe: 14.73±2.96 in AD vs. 16.49±2.15 in controls (P=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86±2.98 in AD vs. 13.70±2.88 in controls (P=0.97); and temporal lobe: 13.31±4.93 in AD vs. 11.07±1.99 in controls (P=0.65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI− mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI− 1.92±1.04 in AD vs. 0.86±0.17 in controls (P=0.54); temporal lobe 2.54±1.59 in AD vs. 0.96±0.11 controls (P=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.
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DOI: 10.1016/S0022-510X(99)00311-1
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title><author><name sortKey="Panegyres, Peter K" sort="Panegyres, Peter K" uniqKey="Panegyres P" first="Peter K." last="Panegyres">Peter K. Panegyres</name><affiliation><mods:affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: peter.panegyres@rph.health.wa.gov.au</mods:affiliation></affiliation></author><author><name sortKey="Zafiris Toufexis, K" sort="Zafiris Toufexis, K" uniqKey="Zafiris Toufexis K" first="K." last="Zafiris-Toufexis">K. Zafiris-Toufexis</name><affiliation><mods:affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</mods:affiliation></affiliation></author><author><name sortKey="Kakulas, B A" sort="Kakulas, B A" uniqKey="Kakulas B" first="B. A." last="Kakulas">B. A. Kakulas</name><affiliation><mods:affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1C71C23F1FD53D686C712657716A59CBD4956243</idno><date when="2000" year="2000">2000</date><idno type="doi">10.1016/S0022-510X(99)00311-1</idno><idno type="url">https://api.istex.fr/document/1C71C23F1FD53D686C712657716A59CBD4956243/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">001704</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title><author><name sortKey="Panegyres, Peter K" sort="Panegyres, Peter K" uniqKey="Panegyres P" first="Peter K." last="Panegyres">Peter K. Panegyres</name><affiliation><mods:affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: peter.panegyres@rph.health.wa.gov.au</mods:affiliation></affiliation></author><author><name sortKey="Zafiris Toufexis, K" sort="Zafiris Toufexis, K" uniqKey="Zafiris Toufexis K" first="K." last="Zafiris-Toufexis">K. Zafiris-Toufexis</name><affiliation><mods:affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</mods:affiliation></affiliation></author><author><name sortKey="Kakulas, B A" sort="Kakulas, B A" uniqKey="Kakulas B" first="B. A." last="Kakulas">B. A. Kakulas</name><affiliation><mods:affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of the Neurological Sciences</title><title level="j" type="abbrev">JNS</title><idno type="ISSN">0022-510X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">173</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="81">81</biblScope><biblScope unit="page" to="92">92</biblScope></imprint><idno type="ISSN">0022-510X</idno></series><idno type="istex">1C71C23F1FD53D686C712657716A59CBD4956243</idno><idno type="DOI">10.1016/S0022-510X(99)00311-1</idno><idno type="PII">S0022-510X(99)00311-1</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-510X</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer’s disease (AD) and experimentally in the brain’s response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI−). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with 35S to detect the two principal splice variants of APP: APP 695 (KPI−) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (n=15) and other neurodegenerative disorders as controls (n=18). The controls consist of frontal lobe atrophy (n=4), Huntington’s disease (n=5), Parkinson’s disease (n=4), motor neuron disease (n=2), multi-infarct dementia (n=1), multisystem atrophy (n=1), and subacute sclerosing panencephalitis (n=1). We have observed no significant differences in the expression of APP 695 KPI– mRNA in frontal lobe: 17.49±3.26 optical density (OD) units of mRNA expression in AD vs. 16.13±1.76 OD units mRNA in controls (P=0.80, linear regression); or temporal lobe: 14.73±2.96 in AD vs. 16.49±2.15 in controls (P=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86±2.98 in AD vs. 13.70±2.88 in controls (P=0.97); and temporal lobe: 13.31±4.93 in AD vs. 11.07±1.99 in controls (P=0.65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI− mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI− 1.92±1.04 in AD vs. 0.86±0.17 in controls (P=0.54); temporal lobe 2.54±1.59 in AD vs. 0.96±0.11 controls (P=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Peter K. Panegyres</name><affiliations><json:string>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</json:string><json:string>E-mail: peter.panegyres@rph.health.wa.gov.au</json:string></affiliations></json:item><json:item><name>K. Zafiris-Toufexis</name><affiliations><json:string>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</json:string></affiliations></json:item><json:item><name>B.A. Kakulas</name><affiliations><json:string>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Neurodegeneration</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>APP</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Gene expression</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>In situ hybridization</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Alzheimer’s disease</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer’s disease (AD) and experimentally in the brain’s response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI−). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with 35S to detect the two principal splice variants of APP: APP 695 (KPI−) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (n=15) and other neurodegenerative disorders as controls (n=18). The controls consist of frontal lobe atrophy (n=4), Huntington’s disease (n=5), Parkinson’s disease (n=4), motor neuron disease (n=2), multi-infarct dementia (n=1), multisystem atrophy (n=1), and subacute sclerosing panencephalitis (n=1). We have observed no significant differences in the expression of APP 695 KPI– mRNA in frontal lobe: 17.49±3.26 optical density (OD) units of mRNA expression in AD vs. 16.13±1.76 OD units mRNA in controls (P=0.80, linear regression); or temporal lobe: 14.73±2.96 in AD vs. 16.49±2.15 in controls (P=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86±2.98 in AD vs. 13.70±2.88 in controls (P=0.97); and temporal lobe: 13.31±4.93 in AD vs. 11.07±1.99 in controls (P=0.65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI− mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI− 1.92±1.04 in AD vs. 0.86±0.17 in controls (P=0.54); temporal lobe 2.54±1.59 in AD vs. 0.96±0.11 controls (P=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.</abstract><qualityIndicators><score>8</score><pdfVersion>1.2</pdfVersion><pdfPageSize>598 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>5</keywordCount><abstractCharCount>2202</abstractCharCount><pdfWordCount>5150</pdfWordCount><pdfCharCount>35858</pdfCharCount><pdfPageCount>12</pdfPageCount><abstractWordCount>330</abstractWordCount></qualityIndicators><title>Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title><pii><json:string>S0022-510X(99)00311-1</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>173</volume><pii><json:string>S0022-510X(00)X0090-1</json:string></pii><pages><last>92</last><first>81</first></pages><issn><json:string>0022-510X</json:string></issn><issue>2</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Journal of the Neurological Sciences</title><publicationDate>2000</publicationDate></host><categories><wos><json:string>CLINICAL NEUROLOGY</json:string><json:string>NEUROIMAGING</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>1999</publicationDate><copyrightDate>2000</copyrightDate><doi><json:string>10.1016/S0022-510X(99)00311-1</json:string></doi><id>1C71C23F1FD53D686C712657716A59CBD4956243</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/1C71C23F1FD53D686C712657716A59CBD4956243/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/1C71C23F1FD53D686C712657716A59CBD4956243/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/1C71C23F1FD53D686C712657716A59CBD4956243/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/1C71C23F1FD53D686C712657716A59CBD4956243/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>2000</date></publicationStmt><notesStmt><note type="content">Fig. 1: Northern analysis on total mRNA extracted from frontal cortex from a patient with Alzheimer’s disease. Approximately 20 μg of RNA were added to each lane and the probes were labelled with 32P. Positions of molecular weight standards are indicated. The size of the APP transcripts measured about 3.2–3.8 kb.</note><note type="content">Fig. 2: Photomicrographs of emulsions from in situ hybridization experiments using antisense, sense, and excess of cold antisense probe to demonstrate the specificity of the in situ hybridization reactions in the frontal cortex of a patient with Alzheimer’s disease (96A/32). Upper left in situ hybridization to APP 695 mRNA using antisense probe, right=excess of cold probe. Lower left in situ hybridization to APP 751 mRNA using antisense probe, right=excess of cold probe, middle=sense probe, right=excess cold probe (×400).</note><note type="content">Fig. 3: In situ hybridization of APP mRNAs from patient 97A/27 with Alzheimer’s disease (×7.8).</note><note type="content">Fig. 4: Photomicrographs of emulsions used from in situ hybridization experiments from the superior temporal gyrus from patient 97A/27 with Alzheimer’s disease. Upper left is APP 695 mRNA (KPI−) stained with H&E and lower left is the negative contrast image. Upper right is APP 757 (KPI+) and lower right is the negative contrast image (×400).</note><note type="content">Table 1: Brain bank diagnostic categories</note><note type="content">Table 2: The sequences of oligonucleotide probes</note><note type="content">Table 3: Demographic data</note><note type="content">Table 4: Standardised optical density units in mRNA expression of APP isoforms in Alzheimer’s disease and other neurodegenerative disorders (OD units=x̄±SEM, n=4 measurements at each data point)</note><note type="content">Table 5: Ratio of OD units of APP mRNA expression in Alzheimer’s disease and other neurodegenerative disorders (APP751/APP695)</note><note type="content">Table 6: APP isoforms in Alzheimer’s disease and other neurodegenerative disorders: Summary. OD units mRNA expression</note><note type="content">Table 7: Published studies of APP mRNA expression in Alzheimer’s disease</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title><author><persName><forename type="first">Peter K.</forename><surname>Panegyres</surname></persName><email>peter.panegyres@rph.health.wa.gov.au</email><note type="correspondence"><p>Corresponding author. Tel.: +61-8-9224-2433; fax: +61-8-9224-2556</p></note><affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</affiliation></author><author><persName><forename type="first">K.</forename><surname>Zafiris-Toufexis</surname></persName><affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</affiliation></author><author><persName><forename type="first">B.A.</forename><surname>Kakulas</surname></persName><affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</affiliation></author></analytic><monogr><title level="j">Journal of the Neurological Sciences</title><title level="j" type="abbrev">JNS</title><idno type="pISSN">0022-510X</idno><idno type="PII">S0022-510X(00)X0090-1</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999"></date><biblScope unit="volume">173</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="81">81</biblScope><biblScope unit="page" to="92">92</biblScope></imprint></monogr><idno type="istex">1C71C23F1FD53D686C712657716A59CBD4956243</idno><idno type="DOI">10.1016/S0022-510X(99)00311-1</idno><idno type="PII">S0022-510X(99)00311-1</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer’s disease (AD) and experimentally in the brain’s response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI−). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with 35S to detect the two principal splice variants of APP: APP 695 (KPI−) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (n=15) and other neurodegenerative disorders as controls (n=18). The controls consist of frontal lobe atrophy (n=4), Huntington’s disease (n=5), Parkinson’s disease (n=4), motor neuron disease (n=2), multi-infarct dementia (n=1), multisystem atrophy (n=1), and subacute sclerosing panencephalitis (n=1). We have observed no significant differences in the expression of APP 695 KPI– mRNA in frontal lobe: 17.49±3.26 optical density (OD) units of mRNA expression in AD vs. 16.13±1.76 OD units mRNA in controls (P=0.80, linear regression); or temporal lobe: 14.73±2.96 in AD vs. 16.49±2.15 in controls (P=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86±2.98 in AD vs. 13.70±2.88 in controls (P=0.97); and temporal lobe: 13.31±4.93 in AD vs. 11.07±1.99 in controls (P=0.65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI− mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI− 1.92±1.04 in AD vs. 0.86±0.17 in controls (P=0.54); temporal lobe 2.54±1.59 in AD vs. 0.96±0.11 controls (P=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Neurodegeneration</term></item><item><term>APP</term></item><item><term>Gene expression</term></item><item><term>In situ hybridization</term></item><item><term>Alzheimer’s disease</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999-11-08">Registration</change><change when="1999-08-20">Modified</change><change when="1999">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>JNS</jid><aid>6291</aid><ce:pii>S0022-510X(99)00311-1</ce:pii><ce:doi>10.1016/S0022-510X(99)00311-1</ce:doi><ce:copyright type="full-transfer" year="2000">Elsevier Science B.V.</ce:copyright></item-info><head><ce:title>Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</ce:title><ce:author-group><ce:author><ce:given-name>Peter K.</ce:given-name><ce:surname>Panegyres</ce:surname><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>peter.panegyres@rph.health.wa.gov.au</ce:e-address></ce:author><ce:author><ce:given-name>K.</ce:given-name><ce:surname>Zafiris-Toufexis</ce:surname></ce:author><ce:author><ce:given-name>B.A.</ce:given-name><ce:surname>Kakulas</ce:surname></ce:author><ce:affiliation><ce:textfn>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +61-8-9224-2433; fax: +61-8-9224-2556</ce:text></ce:correspondence></ce:author-group><ce:date-received day="19" month="5" year="1999"></ce:date-received><ce:date-revised day="20" month="8" year="1999"></ce:date-revised><ce:date-accepted day="8" month="11" year="1999"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer’s disease (AD) and experimentally in the brain’s response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI−). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with <ce:sup loc="pre">35</ce:sup>S to detect the two principal splice variants of APP: APP 695 (KPI−) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (<ce:italic>n</ce:italic>=15) and other neurodegenerative disorders as controls (<ce:italic>n</ce:italic>=18). The controls consist of frontal lobe atrophy (<ce:italic>n</ce:italic>=4), Huntington’s disease (<ce:italic>n</ce:italic>=5), Parkinson’s disease (<ce:italic>n</ce:italic>=4), motor neuron disease (<ce:italic>n</ce:italic>=2), multi-infarct dementia (<ce:italic>n</ce:italic>=1), multisystem atrophy (<ce:italic>n</ce:italic>=1), and subacute sclerosing panencephalitis (<ce:italic>n</ce:italic>=1). We have observed no significant differences in the expression of APP 695 KPI– mRNA in frontal lobe: 17.49±3.26 optical density (OD) units of mRNA expression in AD vs. 16.13±1.76 OD units mRNA in controls (<ce:italic>P</ce:italic>=0.80, linear regression); or temporal lobe: 14.73±2.96 in AD vs. 16.49±2.15 in controls (<ce:italic>P</ce:italic>=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86±2.98 in AD vs. 13.70±2.88 in controls (<ce:italic>P</ce:italic>=0.97); and temporal lobe: 13.31±4.93 in AD vs. 11.07±1.99 in controls (<ce:italic>P</ce:italic>=0.65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI− mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI− 1.92±1.04 in AD vs. 0.86±0.17 in controls (<ce:italic>P</ce:italic>=0.54); temporal lobe 2.54±1.59 in AD vs. 0.96±0.11 controls (<ce:italic>P</ce:italic>=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Neurodegeneration</ce:text></ce:keyword><ce:keyword><ce:text>APP</ce:text></ce:keyword><ce:keyword><ce:text>Gene expression</ce:text></ce:keyword><ce:keyword><ce:text>In situ hybridization</ce:text></ce:keyword><ce:keyword><ce:text>Alzheimer’s disease</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders</title></titleInfo><name type="personal"><namePart type="given">Peter K.</namePart><namePart type="family">Panegyres</namePart><affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</affiliation><affiliation>E-mail: peter.panegyres@rph.health.wa.gov.au</affiliation><description>Corresponding author. Tel.: +61-8-9224-2433; fax: +61-8-9224-2556</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">K.</namePart><namePart type="family">Zafiris-Toufexis</namePart><affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B.A.</namePart><namePart type="family">Kakulas</namePart><affiliation>Department of Neuropathology, Royal Perth Hospital, Perth 6000, Western Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1999</dateIssued><dateValid encoding="w3cdtf">1999-11-08</dateValid><dateModified encoding="w3cdtf">1999-08-20</dateModified><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Differential expression of the amyloid precursor protein gene (APP) may be important in the development of amyloidosis in Alzheimer’s disease (AD) and experimentally in the brain’s response to injury. Controversial data suggests that APP isoforms containing the Kunitz protease inhibitor isoform (APP KPI+) are over expressed in the brains of patients with AD when compared to the non-Kunitz protease inhibitor containing isoforms (APP KPI−). We have investigated this hypothesis using a quantitative analysis of gene expression on brain tissue collected at post-mortem. In situ hybridization has been used with synthetic oligonucleotide probes labelled with 35S to detect the two principal splice variants of APP: APP 695 (KPI−) and APP 751 (KPI+). A prospective brain bank of frozen brain specimens has been established and includes pathologically proven AD (n=15) and other neurodegenerative disorders as controls (n=18). The controls consist of frontal lobe atrophy (n=4), Huntington’s disease (n=5), Parkinson’s disease (n=4), motor neuron disease (n=2), multi-infarct dementia (n=1), multisystem atrophy (n=1), and subacute sclerosing panencephalitis (n=1). We have observed no significant differences in the expression of APP 695 KPI– mRNA in frontal lobe: 17.49±3.26 optical density (OD) units of mRNA expression in AD vs. 16.13±1.76 OD units mRNA in controls (P=0.80, linear regression); or temporal lobe: 14.73±2.96 in AD vs. 16.49±2.15 in controls (P=0.55). No significant differences have been found in APP 751 KPI+ in frontal lobe: 12.86±2.98 in AD vs. 13.70±2.88 in controls (P=0.97); and temporal lobe: 13.31±4.93 in AD vs. 11.07±1.99 in controls (P=0.65). Analysis of the ratios of APP 751 KPI+ OD units of mRNA to APP 695 KPI− mRNA revealed a trend to an increased ratio which did not reach statistical significance: frontal lobe APP 751 KPI+/APP 695 KPI− 1.92±1.04 in AD vs. 0.86±0.17 in controls (P=0.54); temporal lobe 2.54±1.59 in AD vs. 0.96±0.11 controls (P=0.34). Our data has not revealed differential expression of APP mRNA isoforms in AD and supports the hypothesis that post-translational events in APP metabolism are important in amyloidogenesis and the pathogenesis of AD.</abstract><note type="content">Fig. 1: Northern analysis on total mRNA extracted from frontal cortex from a patient with Alzheimer’s disease. Approximately 20 μg of RNA were added to each lane and the probes were labelled with 32P. Positions of molecular weight standards are indicated. The size of the APP transcripts measured about 3.2–3.8 kb.</note><note type="content">Fig. 2: Photomicrographs of emulsions from in situ hybridization experiments using antisense, sense, and excess of cold antisense probe to demonstrate the specificity of the in situ hybridization reactions in the frontal cortex of a patient with Alzheimer’s disease (96A/32). Upper left in situ hybridization to APP 695 mRNA using antisense probe, right=excess of cold probe. Lower left in situ hybridization to APP 751 mRNA using antisense probe, right=excess of cold probe, middle=sense probe, right=excess cold probe (×400).</note><note type="content">Fig. 3: In situ hybridization of APP mRNAs from patient 97A/27 with Alzheimer’s disease (×7.8).</note><note type="content">Fig. 4: Photomicrographs of emulsions used from in situ hybridization experiments from the superior temporal gyrus from patient 97A/27 with Alzheimer’s disease. Upper left is APP 695 mRNA (KPI−) stained with H&E and lower left is the negative contrast image. Upper right is APP 757 (KPI+) and lower right is the negative contrast image (×400).</note><note type="content">Table 1: Brain bank diagnostic categories</note><note type="content">Table 2: The sequences of oligonucleotide probes</note><note type="content">Table 3: Demographic data</note><note type="content">Table 4: Standardised optical density units in mRNA expression of APP isoforms in Alzheimer’s disease and other neurodegenerative disorders (OD units=x̄±SEM, n=4 measurements at each data point)</note><note type="content">Table 5: Ratio of OD units of APP mRNA expression in Alzheimer’s disease and other neurodegenerative disorders (APP751/APP695)</note><note type="content">Table 6: APP isoforms in Alzheimer’s disease and other neurodegenerative disorders: Summary. OD units mRNA expression</note><note type="content">Table 7: Published studies of APP mRNA expression in Alzheimer’s disease</note><subject><genre>Keywords</genre><topic>Neurodegeneration</topic><topic>APP</topic><topic>Gene expression</topic><topic>In situ hybridization</topic><topic>Alzheimer’s disease</topic></subject><relatedItem type="host"><titleInfo><title>Journal of the Neurological Sciences</title></titleInfo><titleInfo type="abbreviated"><title>JNS</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">20000215</dateIssued></originInfo><identifier type="ISSN">0022-510X</identifier><identifier type="PII">S0022-510X(00)X0090-1</identifier><part><date>20000215</date><detail type="volume"><number>173</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue pages"><start>81</start><end>166</end></extent><extent unit="pages"><start>81</start><end>92</end></extent></part></relatedItem><identifier type="istex">1C71C23F1FD53D686C712657716A59CBD4956243</identifier><identifier type="DOI">10.1016/S0022-510X(99)00311-1</identifier><identifier type="PII">S0022-510X(99)00311-1</identifier><accessCondition type="use and reproduction" contentType="">© 2000Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science B.V., ©2000</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/1C71C23F1FD53D686C712657716A59CBD4956243/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">CLINICAL NEUROLOGY</classCode><classCode scheme="WOS">NEUROIMAGING</classCode><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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