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Title: The role of Clusterin/apolipoprotein J and HDL functionality in Alzheimer's disease and mild cognitive impairment
Author: Mullan, Gemma
ISNI:       0000 0004 5372 6200
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2014
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The CLU gene is associated with Alzheimer's disease (AD). With its protein, clusterin, having the ability to bind to various ligands, such as amyloid beta, thus it has become a worthy target in AD research Therefore, the focus of this thesis was to investigate the implications of clusterin within mild cognitive impairment (MCI) and AD. Aims and Objectives This thesis encompassed four main studies. The first investigated if SNP rs11136000 influenced plasma clusterin in MCI and AD, compared to an age-matched cognitively healthy control group. The second study assessed if plasma soluble receptors (sLRP1 and sLRP2) were related to clusterin in MCI and AD. The third was a method development study to isolate high-density lipoproteins (HDL) from smaller volumes of plasma than previously used. The fourth study investigated if the function of HDL was altered by MCI and AD. Results In the first study, plasma clusterin levels were higher in the MCI and AD groups, compared to the control group, with the MCI group having the highest levels. In the second study, although sLRP1 were similar, sLRP2 decreased in the AD group, compared to the control and MCI groups. The third study showed that HDL could be isolated from a smaller volume of plasma without loss of detection ability. The final study identified increased SAA and decreased clusterin and LCAT inAD. Discussion and Conclusion Overall, this thesis has demonstrated various clusterin and soluble receptor-related changes in those with cognitive decline and that the presence of AD influenced the proatherogenic phenotype of HDL. In conclusion, observing such changes in cognitive decline may be useful biomarkers, as well as targets for therapies towards delaying the onset of such an irreversible disorder.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available