Foiani, Martha;
(2020)
Investigating novel tau biomarkers for frontotemporal dementia.
Doctoral thesis (Ph.D), UCL (University College London).
Abstract
Introduction: Frontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathological inclusions. Currently, there are no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed to investigate the potential of novel tau species as biomarkers for tau pathology in FTD. Method: Three levels of investigations were carried out: 1) established tau biomarkers and novel tau species were measured in cerebrospinal fluid (CSF) and blood samples from FTD case; 2) tau inclusions were immunohistochemically profiled with a range of antibodies; 3) proteomic differences in homogenised brain samples and laser-captured tau inclusions were investigated with mass spectrometry techniques. Results: Results show that although some novel tau species were significantly different between FTD and healthy controls none show promise as a biomarker for FTD. Tau inclusions epitope profiling identified three antibodies that selectively bind specific tauopathies. Proteomic differences were present across tau pathologies linked to FTD and further experiments are needed to validate these. Conclusions: Despite the reliability of tau biomarkers for AD-related tau pathology, poor diagnostic utility is offered in FTD by currently established tau species. The quest for in vivo markers of FTLD-tau pathology continues.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating novel tau biomarkers for frontotemporal dementia |
| Event: | UCL |
| Language: | English |
| Additional information: | Copyright © The Author 2020. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/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 UCL > Provost and Vice Provost Offices 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 Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10107535 |
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