METABOLOMICS IN ALZHEIMER'S DISEASE

Abstract

Metabolites are a potentially useful source of detecting and identifying disease specific biomarkers. This thesis investigates the possibility of using metabolomics applications to detect Alzheimer's disease associated metabolite peaks in patients and to detect longitudinal changes of the disease. Serum samples and clinical data were collected from 60 healthy controls and 60 Alzheimer's disease patients (60 at baseline and 60 at 12 month follow-up). The metabolic fingerprinting of serum samples using the FT-IR lacked discriminatory power to discriminate Alzheimer's disease and non-disease samples due to the similar magnitude of biological and analytical variation. The metabolic profiling of serum samples using the GC-ToF-MS did not reveal any significantly altered metabolite peaks between the Alzheimer's disease and non-disease groups. Metabolic profiling of serum samples using the UPLC-LTQ/Orbitrap-MS operated in the positive ionisation mode did not reveal any significantly altered metabolite peaks between the disease and non-disease groups. Up to twelve metabolite peaks were significantly altered in the Alzheimer's disease baseline and follow-up samples, indicating a potential association with disease progression. Metabolic profiling of serum samples using the UPLC-LTQ/Orbitrap-MS operated in the negative ionisation mode did not reveal any significantly altered metabolite peaks between Alzheimer's disease and non-disease groups. Three metabolite peaks were significantly altered in the Alzheimer's disease baseline and follow-up samples, indicating a potential association with disease progression. Metabolic profiling of serum samples with the UPLC-LTQ/Orbitrap-MS may potentially be used to detect disease and disease progression associated metabolite peaks. The metabolite peaks require identification followed by a validation experiment.

Date of Award	1 Aug 2013
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Nitin Purandare (Supervisor) & Alistair Burns (Supervisor)