Investigating the biological effects of (nano)particles in Alzheimer’s disease pathologies

Fleming, Charlotte L.

Investigating the biological effects of (nano)particles in Alzheimer’s disease pathologies

Fleming, Charlotte L.

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Publication Type:: Thesis
Issue Date:: 2022

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Field	Value	Language
dc.contributor.author	Fleming, Charlotte L.
dc.date.accessioned	2023-03-06T02:32:02Z
dc.date.available	2023-03-06T02:32:02Z
dc.date.issued	2022
dc.identifier.uri	http://hdl.handle.net/10453/166679
dc.description	University of Technology Sydney. Faculty of Science.	en_US.UTF-8
dc.description.abstract	Alzheimer’s disease (AD) is the most common form of dementia, with sporadic AD accounting for over 95% of cases and thought to be influenced by lifestyle and environmental factors. Magnetite pollutant particles have been found in abundance in brains of people with AD in densely populated cities. This observation highlighted the need for increased understanding of the potential impact on human health. Therefore, chapter 3 commenced an extensive systematic and bibliometric analytical review of the characteristics and applications of magnetite from 1990-2020, identifying the formation and broad applications in environmental, industrial, and biomedical fields, also highlighting the cytotoxic effects from overuse as a biomedicine and its potential implication in neurodegeneration and AD as an air pollutant. Subsequently, chapter 4 explored the biological effects that air pollutants (iron, diesel and magnetite) have on AD pathologies. This study showed air pollutants, particularly magnetite, increased anxiety, stress, and cognitive impairment, and increased neuronal cell loss in the hippocampus of the double transgenic APP/PS1 and W/T mice. Air pollutants also increased amyloid plaques and inflammation, in both the in vivo and in vitro models, neuroblastoma SH-SY5Y cells, with oxidative stress found to be induced via NFB pathway, suggesting a global inflammatory response that occurs through activated microglial and astrocytes. The current therapies for AD, while effective in managing symptoms do not delay or reverse disease progression. Oxidative stress is a central process in AD pathogenesis therefore the antioxidant, cerium oxide has emerged as a potential therapy. Cerium oxide has been used as a biomedicine for cancer therapy and ischemic stroke, however not for AD. This inspired the systematic and bibliometric review on cerium oxide from 1990-2020 (chapter 5), bringing to light the catalytic and redox properties used for innumerable environmental/industrial and biomedical applications. The advanced nanotechnology engineering was a focus in increasing nanoparticle efficiency for a wide range of applications, including AD. Consequently, because air pollutant magnetite induces AD pathologies, chapter 6 explored if cerium oxide nanoparticles could delay or reverse this. Cerium oxide nanoparticles decreased cognitive impairment, neuronal death, amyloid-beta species formation and inflammation in the APP/PS1 and W/T mice, and decreased inflammation and oxidative stress in SH-SH5Y and microglial BV-2 cells. In summary, air pollutants induce neurological changes associated with AD, and after exposure to cerium oxide nanoparticles these changes are delayed or reversed. Overall, this study concludes that cerium oxide nanoparticles are promising potential therapeutics for air pollutant induced AD pathologies.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/166679/2/02whole.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2022 Charlotte Fleming
dc.rights	au.edu.uts.lib/ppc
dc.title	Investigating the biological effects of (nano)particles in Alzheimer’s disease pathologies	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Alzheimer’s disease (AD) is the most common form of dementia, with sporadic AD accounting for over 95% of cases and thought to be influenced by lifestyle and environmental factors. Magnetite pollutant particles have been found in abundance in brains of people with AD in densely populated cities. This observation highlighted the need for increased understanding of the potential impact on human health. Therefore, chapter 3 commenced an extensive systematic and bibliometric analytical review of the characteristics and applications of magnetite from 1990-2020, identifying the formation and broad applications in environmental, industrial, and biomedical fields, also highlighting the cytotoxic effects from overuse as a biomedicine and its potential implication in neurodegeneration and AD as an air pollutant. Subsequently, chapter 4 explored the biological effects that air pollutants (iron, diesel and magnetite) have on AD pathologies. This study showed air pollutants, particularly magnetite, increased anxiety, stress, and cognitive impairment, and increased neuronal cell loss in the hippocampus of the double transgenic APP/PS1 and W/T mice. Air pollutants also increased amyloid plaques and inflammation, in both the in vivo and in vitro models, neuroblastoma SH-SY5Y cells, with oxidative stress found to be induced via NFB pathway, suggesting a global inflammatory response that occurs through activated microglial and astrocytes. The current therapies for AD, while effective in managing symptoms do not delay or reverse disease progression. Oxidative stress is a central process in AD pathogenesis therefore the antioxidant, cerium oxide has emerged as a potential therapy. Cerium oxide has been used as a biomedicine for cancer therapy and ischemic stroke, however not for AD. This inspired the systematic and bibliometric review on cerium oxide from 1990-2020 (chapter 5), bringing to light the catalytic and redox properties used for innumerable environmental/industrial and biomedical applications. The advanced nanotechnology engineering was a focus in increasing nanoparticle efficiency for a wide range of applications, including AD. Consequently, because air pollutant magnetite induces AD pathologies, chapter 6 explored if cerium oxide nanoparticles could delay or reverse this. Cerium oxide nanoparticles decreased cognitive impairment, neuronal death, amyloid-beta species formation and inflammation in the APP/PS1 and W/T mice, and decreased inflammation and oxidative stress in SH-SH5Y and microglial BV-2 cells. In summary, air pollutants induce neurological changes associated with AD, and after exposure to cerium oxide nanoparticles these changes are delayed or reversed. Overall, this study concludes that cerium oxide nanoparticles are promising potential therapeutics for air pollutant induced AD pathologies.

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