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- Preece, Paul, et al.
(författare)
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Amyloid precursor protein mRNA levels in Alzheimer's disease brain
- 2004
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Ingår i: Brain Research. Molecular Brain Research. - : Elsevier BV. - 0169-328X .- 1872-6941. ; 122:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Insoluble beta-amyloid deposits in Alzheimer's disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls (p=0.002). There was no change in the mRNA levels of KPI-(APP 695) (p=0.898). Therefore, whilst KPI-mRNA levels remained stable the KPI(+) species increased specifically in the AD brains.
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| 3. |
- Preece, Paul, et al.
(författare)
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An optimistic view for quantifying mRNA in post-mortem human brain
- 2003
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Ingår i: Brain Research. Molecular Brain Research. - 0169-328X .- 1872-6941. ; 116:1-2, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative human mRNA data are derived from post-mortem or biopsied tissue. RNA degradation, poor replication, a large mRNA variance and confounding factors such as brain pH and age of death are often cited, however, as objections to the data's reliability. A central question is whether post-mortem human mRNA can be treated as a statistically ordered system. TaqMan real-time RT-PCR was used to measure seven mRNAs in 513 cortical samples taken from 90 Alzheimer's disease and 81 control brains. Despite a high mRNA variance strong correlations were found between the mRNA transcripts in a single brain. Where a brain has a high/low level of one mRNA, the same brain invariably has a high/low level of other mRNAs; correlated order is present and allows removal of that source of variation common to all genes. Although levels of mRNA are highly variable between subjects (>1000-fold), quantitative order is present in post-mortem human mRNA, allowing effects due to pathology or gender to be isolated and tested for significance.
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| 4. |
- Preece, Paul, et al.
(författare)
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Beta-secretase (BACE) and GSK-3 mRNA levels in Alzheimer's disease
- 2003
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Ingår i: Brain Research. Molecular Brain Research. - 0169-328X .- 1872-6941. ; 116:1-2, s. 155-158
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Tidskriftsartikel (refereegranskat)abstract
- Beta-secretase (BACE) and glycogen synthase kinase (GSK 3) are two enzymes thought to play a role in Alzheimer's disease. We extracted mRNA from 90 Alzheimer and 81 control brains. Levels of mRNA were quantified for BACE and GSK 3 with TaqMan real-time RT-PCR. We found no change in the Alzheimer's disease brains relative to controls for either the BACE or the GSK 3alpha mRNA levels.
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