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Title: Brain metabolomics : a new comprehensive metabolic profiling approach to Alzheimer's disease pathology using LC-MS and GC-MS
Author: Ebshiana, Amera Abugiala A.
ISNI:       0000 0004 7656 3651
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2018
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Alzheimer’s disease (AD) is the most common form of dementia characterized by memory loss and other cognitive abilities that worsen overtime to interfere with daily life. AD’s incidence and financial burden is rapidly increasing worldwide. Considering brain disease pathology starts 20 years before symptoms become noticeable, detecting molecules capable of precise diagnosis of disease before development of symptoms is a priority. This thesis investigates the possibility of using metabolomics to detect AD associated metabolites and to measure the abundance of a range of small molecule metabolites in human brain to examine how these metabolites are associated with severity of AD pathology and expression of symptoms. A project plan was designed to investigate brain metabolic profiling of AD samples. Initially rat brain samples were used to develop a method capable of the coverage of a wide range of metabolites using Liquid chromatography quadrupole time of flight mass spectrometry (LC- Q-TOF-MS) combining two separation techniques reversed phase (RP) and Hydrophilic liquid chromatography (HILIC). After this, gas chromatography mass spectrometry (GC-MS) analysis was employed with the aim of developing untargeted analysis and expanding the metabolome, thus identifying new and novel AD predictor metabolites to help elucidate and understand brain metabolism. Later, a brain invial dual extraction (IVDE) method was tested and applied to plasma of control and AD groups using a multimodal strategy that combines both LC-MS and GC-MS data. Finally, human brain samples from control, asymptomatic and AD patients were analysed using the developed untargeted LC&GC-MS brain IVDE method. Results revealed unsaturated fatty acids and sphingolipid metabolism to be significantly dysregulated in the brains of patients with varying degrees of Alzheimer pathology.
Supervisor: Legido Quigley, Cristina ; Parsons, Richard Bramwell Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available