Alawode, Deborah Oluwadamilola;
(2024)
Developing Novel Supersensitive Fluid Biomarker Assays for Neurodegenerative Diseases.
Doctoral thesis (Ph.D), UCL (University College London).
Preview |
Text
Alawode_10193460_Thesis.pdf Download (4MB) | Preview |
Abstract
Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia worldwide. In recent years, there has been a shift in the diagnostic methodology used from a purely symptoms-based to a more holistic criteria, which incorporates both neuroimaging and fluid biomarkers. Whilst previously, cerebrospinal fluid (CSF) biomarkers dominated the AD fluid biomarker territory, the recent update to the ‘ATXN’ diagnostic criteria has seen the addition of blood-based biomarkers. Whilst for AD biomarkers like phosphorylated tau, plasma measurements have shown a similarly strong diagnostic accuracy to their CSF counterparts, the same cannot be said for the main measure of amyloid-β (Aβ) pathology, the Aβ42/Aβ40 ratio (Aβ42/40), with several studies observing extensive overlap between diagnostic groups in plasma, most likely due to the peripheral production of Aβ. As such, there is a need for more robust Aβ biomarkers which better distinguish between diagnostic groups. Two such biomarkers worth investigating are pyroglutamate-modified Aβ (AβpE), which is a plaque-specific form of Aβ, and Aβ43. Although in the past, plasma biomarker measurements were limited by the analytical sensitivity of instruments available, recent advances in technology, particularly the development of Single molecule array (Simoa), have mitigated this limitation. Yet, there is evidently still a sensitivity issue plaguing the scientific world and the fluid biomarker space, given that Aβ43 has yet to be measured in blood, and AβpE has not successfully been measured in either CSF or blood. In this thesis, we independently assess the performance of AD CSF and plasma biomarkers, particularly focusing on the diagnostic performance of Aβ42/40. Alongside this, we validate the increased sensitivity of a protype upgrade to the standard Simoa instrument, termed the ‘SRx Pro’. On the basis of these results, we describe the process of developing novel Simoa assays for the detection of Aβ43 and AβpE.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Developing Novel Supersensitive Fluid Biomarker Assays for Neurodegenerative Diseases |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2024. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10193460 |
Archive Staff Only
 |
View Item |
