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Title: Application of the L-Tryptophanol assay as an indicator of soluble amyloid aggregates in brain, CSF and plasma
Author: Jones, Glynn
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2017
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Alzheimer's disease (AD) is the most common cause of dementia; a problem that is growing in size and cost as the population ages. Early soluble aggregates composed misfolded 'amyloid' peptide sequences have been implicated as key to the initiation and onset of AD pathology, although little is definitively known as to when and how these assemblies form or interact to instigate pathology. The primary focus of this study was to evaluate whether L-Tryptophanol (Trol) signal, which has been shown to be induced via soluble amyloid species, increases with AD severity in a range of ex vivo human samples. Testing of this hypothesis was carried out in several stages: Initially synthetic versions of the amyloid beta (Aβ) peptide were tested in vitro to corroborate Trols propensity to associate to amyloid assemblies and allow for method development. Next, a range of brain lysates from several transgenic mouse lines and aged human AD cases and controls were assessed using the reporter. These experiments demonstrated Trols sensitivity to Aβ and tau, and provided compelling evidence that Trol signal tracks disease progression in brain lysates. During the final stage of testing cerebrospinal fluid (CSF) from AD and Parkinson's disease (PD) patients, and blood plasma samples from PD patients was evaluated. Results from this phase of testing indicated that Trol was able to detect differences in sample composition between healthy and diseased individuals, however differences were not clear cut and could have been affected by confounding factors. Overall, the data presented here suggest that Trol may be able to track disease progression in amyloidopathies when implemented in brain lysates. However, further testing is required to completely validate this finding. These findings highlight the potential of simple techniques for amyloid detection to aid within the diagnosis, evaluation of disease progression and study of AD and other neurodegenerative diseases.
Supervisor: Not available Sponsor: University of Aberdeen Development Trust ; Alzheimer's Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Amyloid ; Alzheimer's disease ; Brain ; Cerebrospinal fluid ; Plasma ; Aggregation (Chemistry)