Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders
Identifieur interne : 001B42 ( Main/Exploration ); précédent : 001B41; suivant : 001B43Amyloid precursor protein gene isoforms in Alzheimer’s disease and other neurodegenerative disorders
Auteurs : Peter K. Panegyres [Australie] ; K. Zafiris-Toufexis [Australie] ; B. A. Kakulas [Australie]Source :
- 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.
Url:
DOI: 10.1016/S0022-510X(99)00311-1
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Kakulas</name></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><idno type="wicri:Area/Main/Curation">001468</idno><idno type="wicri:Area/Main/Exploration">001B42</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 wicri:level="2"><country>Australie</country><placeName><region type="state">Australie-Occidentale</region></placeName><wicri:cityArea>Department of Neuropathology, Royal Perth Hospital, Perth 6000</wicri:cityArea></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Australie</country></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 wicri:level="2"><country>Australie</country><placeName><region type="state">Australie-Occidentale</region></placeName><wicri:cityArea>Department of Neuropathology, Royal Perth Hospital, Perth 6000</wicri:cityArea></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 wicri:level="2"><country>Australie</country><placeName><region type="state">Australie-Occidentale</region></placeName><wicri:cityArea>Department of Neuropathology, Royal Perth Hospital, Perth 6000</wicri:cityArea></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><affiliations><list><country><li>Australie</li></country><region><li>Australie-Occidentale</li></region></list><tree><country name="Australie"><region name="Australie-Occidentale"><name sortKey="Panegyres, Peter K" sort="Panegyres, Peter K" uniqKey="Panegyres P" first="Peter K." last="Panegyres">Peter K. Panegyres</name></region><name sortKey="Kakulas, B A" sort="Kakulas, B A" uniqKey="Kakulas B" first="B. A." last="Kakulas">B. A. Kakulas</name><name sortKey="Panegyres, Peter K" sort="Panegyres, Peter K" uniqKey="Panegyres P" first="Peter K." last="Panegyres">Peter K. Panegyres</name><name sortKey="Zafiris Toufexis, K" sort="Zafiris Toufexis, K" uniqKey="Zafiris Toufexis K" first="K." last="Zafiris-Toufexis">K. 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