A population-based study of cognitive decline and peripheral inflammatory gene expression

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A population-based study of cognitive decline and peripheral inflammatory gene expression

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dc.contributor.author Bradley-Smith, Rachel Mary en_US
dc.date.accessioned 2011-12-06T18:29:15Z en_US
dc.date.accessioned 2013-03-20T18:42:08Z
dc.date.issued 2011-09-29 en_US
dc.description.abstract Neuroinflammation has a key role in the pathology of cognitive decline. This study sought to determine whether peripherally expressed inflammatory transcripts had significant associations with cognitive performance or cognitive decline, using genome-wide and focussed candidate gene analyses. The study used data from 691 participants from the InCHIANTI study of ageing. Participants had undertaken Mini-Mental State Examinations at enrolment and at year 9 of follow-up, and provided peripheral whole blood samples for RNA extraction at year 9. Global gene expression data was generated using the Illumina Human HT12 BeadChip microarray. The study analysed global and inflammatory-focussed gene expression associations with cognitive performance and decline, and gene pathway associations with cognitive performance/decline. A candidate-driven RT-PCR expression quantitative trait locus (eQTL) analysis was also performed to determine whether genetic variants associated with cognitive decline affected gene expression abundance in association with phenotypic variation. Raised expression of a single transcript, C-C chemokine receptor 2 (CCR2), had a significant association with poor cognitive performance at global expression analysis and with both cognitive performance and cognitive decline in focussed inflammatory subset analysis. Expression of CCR2 in transgenic animals has previously been associated with both cortical Alzheimer disease pathology and peripheral vascular disease. eQTL analysis identified five significant eQTLs for local genes but no significant associations between peripheral expression of these genes and cognitive decline. This study’s analyses present little evidence that peripheral inflammatory gene expression is playing a significant role in cognitive impairment or preceding 9-year cognitive decline in this cohort. Only one inflammatory transcript (CCR2) was significantly associated with cognitive impairment at genome-wide analysis. The CCR2 knockout mouse has been shown to have Alzheimer’s-like pathology; results of this study indicate that the mouse model may have relevance for the human population. en_GB
dc.identifier.uri http://hdl.handle.net/10036/3298 en_US
dc.language.iso en en_GB
dc.publisher University of Exeter en_GB
dc.subject Cognitive decline en_GB
dc.subject Alzheimer en_GB
dc.subject eQTL en_GB
dc.subject Neuroinflammation en_GB
dc.title A population-based study of cognitive decline and peripheral inflammatory gene expression en_GB
dc.type Thesis or dissertation en_GB
dc.date.available 2011-12-06T18:29:15Z en_US
dc.date.available 2013-03-20T18:42:08Z
dc.contributor.advisor Littlechild, Jennifer en_US
dc.contributor.advisor Harries, Lorna en_US
dc.publisher.department Biosciences en_GB
dc.type.degreetitle MbyRes in Biosciences en_GB
dc.type.qualificationlevel Masters Degree en_GB
dc.type.qualificationname MbyRes en_GB


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