The aim of this thesis was to optimise a method for the unequivocal identification of aluminium (Al) in human brain tissue. The second aim was to devise a protocol that was simple to implement and as such could be carried out without the need for sophisticated and expensive instrumentation. The presence of Al in brain tissue is linked to a number of neurodegenerative diseases and is the cause of dialysis encephalopathy. Therefore, it is of paramount importance to be able to both measure and locate Al in complex milieu such as human brain tissues. Multiple methods have been proposed for the identification of Al in biota including human tissues. However, there have been limitations within these methods such as specificity, selectivity and limits of detection. Herein, transversely heated graphite atomic absorption spectrometry (TH GFAAS) and fluorescence microscopy were used to measure and locate Al within brain tissues of donors who died with a diagnosis of familial Alzheimer’s disease (fAD) or autism. A fluorimetric method was optimised using surrogate human tissues so as not to use actual human brain tissue for method development. The results identified lumogallion as a selective and specific fluorophore for the identification of Al. The complex of lumogallion with Al produced characteristic orange fluorescence, which was specific to Al and for which there were no interferences from other metals which could be present in tissue, e.g. calcium, magnesium, iron. Congo red was used to identify the presence of amyloid, which was confirmed as being in a sheet confirmation by the presence of apple-green birefringence. Lumogallion was used successfully and unequivocally to demonstrate the presence and location of Al within all four main lobes of brain tissue donated by individuals with a diagnosis of fAD. The combination of TH GFAAS and fluorescence microscopy was used to provide the first evidence of Al in the brains of individuals with fAD and these results should be considered in the light of the suggested role of Al in all forms of Alzheimer’s disease.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:721629 |
| Date | January 2017 |
| Creators | Mirza, Ambreen |
| Publisher | Keele University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.keele.ac.uk/3866/ |
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