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Sökning: WFRF:(Cairns Nigel J)

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11.
  • Preece, Paul, et al. (författare)
  • Amyloid precursor protein mRNA levels in Alzheimer's disease brain
  • 2004
  • Ingår i: Brain Research. Molecular Brain Research. - : Elsevier BV. - 0169-328X .- 1872-6941. ; 122:1, s. 1-9
  • 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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12.
  • Preece, Paul, et al. (författare)
  • An optimistic view for quantifying mRNA in post-mortem human brain
  • 2003
  • Ingår i: Brain Research. Molecular Brain Research. - 0169-328X .- 1872-6941. ; 116:1-2, s. 7-16
  • 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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13.
  • Preece, Paul, et al. (författare)
  • Beta-secretase (BACE) and GSK-3 mRNA levels in Alzheimer's disease
  • 2003
  • Ingår i: Brain Research. Molecular Brain Research. - 0169-328X .- 1872-6941. ; 116:1-2, s. 155-158
  • 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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15.
  • Cairns, Mathew J., et al. (författare)
  • Tetraethylorthosilicate-containing barrier dispersion coatings-Mechanism of action
  • 2020
  • Ingår i: Progress in organic coatings. - : Elsevier. - 0300-9440 .- 1873-331X. ; 139
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate the use of tetraethylorthosilicate (TEOS) as a silica precursor for water barrier poly(styrenebutadiene) latex dispersion coating applications. The TEOS is adsorbed at the surface interface by the latex particles in the aqueous dispersion due to the hydrophobic nature of the surface and the TEOS. It then undergoes hydrolysis and condensation to the silica phase in the interstitial sites in the partially dry close-packed polymer structure. The fully cured film exhibits a greater degree of coalescence than films prepared from the unmodified latex binder. Large discrete silica particles are not formed within the cured film; rather the films contain homogenous silica dispersion with a probable particle size no larger than 10 nm. This higher degree of coalescence results in improvements in water vapour barrier performance from 121 - 20 g m(-2) d(-1), with direct water barrier performance (Cobb 120 s) improving from 25 to < 2 g m(-2), compared to the silica-free film.
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16.
  • Crary, John F., et al. (författare)
  • Primary age-related tauopathy (PART) : a common pathology associated with human aging
  • 2014
  • Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 755-766
  • Tidskriftsartikel (refereegranskat)abstract
    • We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A beta) plaques. For these "NFT+/A beta-aEuroe brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A beta accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
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17.
  • Guerreiro, Rita, et al. (författare)
  • Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.
  • 2016
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 38, s. 7-214
  • Tidskriftsartikel (refereegranskat)abstract
    • The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.
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  • Resultat 11-20 av 28
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