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Functional-biochemical relationships in the posterior cingulate cortex, and their application to the genetic risk of Alzheimer’s disease

Costigan, Alison 2016. Functional-biochemical relationships in the posterior cingulate cortex, and their application to the genetic risk of Alzheimer’s disease. PhD Thesis, Cardiff University.
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A major challenge in Alzheimer’s disease (AD) research is to improve understanding of the earliest brain changes associated with AD, in order to develop treatments to combat this disease. One strategy potentially able to inform this need is the study of brain regions associated with AD in young adults at genetic risk of AD. A key region of increasing interest to AD researchers is the posterior cingulate cortex (PCC). Despite being implicated in AD pathogenesis, its function is not well understood. Neuroimaging studies in young adults who carry the strongest genetic risk factor for AD, the Apolipoprotein (APOE) E4 allele, have detected glucose metabolism, activity and functional connectivity alterations in the PCC. A better understanding of PCC function would aid interpretation of these changes, to improve insight into AD pathogenesis. This thesis applied functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) to study PCC activity correlates with brain metabolites in vivo (Chapters 3 and 4), prior to investigating whether these metabolites might be altered in APOE-E4 carriers aged 18-25 years (Chapter 5). Chapters 3 and 4 detected a category-sensitive fMRI response and fMRI-MRS relationship for the scene condition of a perception task and a working memory task, specifically a positive correlation between PCC activity and the metabolite N-acetyl- aspartate (tNAA), a marker of neuronal integrity associated with neuronal mitochondrial metabolism. The scene conditions of these paradigms previously elicited an altered pattern of PCC activity in young APOE-E4 carriers. Chapter 5 therefore compared PCC tNAA and other MRS metabolites between young APOE-E4 carriers and non-carriers. No MRS differences, however, were evident between APOE groups. These findings contribute to our understanding of the biochemistry underpinning PCC activity, but suggest that an alteration in such a pathway may not be linked with the activity alterations detected in young APOE-E4 carriers.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Date of First Compliant Deposit: 17 May 2017
Date of Acceptance: 16 May 2017
Last Modified: 01 Jun 2018 01:30

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