Exploration of novel biomarkers in frontotemporal lobar degeneration

Abstract

Frontotemporal lobar degeneration is a neurodegenerative disorder characterised by progressive deterioration of frontal and anterior temporal lobes of the brain. It can be divided into a number of distinct clinical syndromes including semantic variant of primary progressive aphasia, non-fluent variant of primary progressive aphasia, progressive supranuclear palsy, corticobasal syndrome and behavioural variant frontotemporal dementia.

Currently, there are no available treatments for these clinical syndromes. Previous efforts to investigate and develop targeted disease modifying therapies for these conditions have been hampered by a lack of biomarkers that would aid in diagnosis and assessment of disease progression. In this work, I have focused on identifying and examining potential biomarkers across frontotemporal lobar degeneration syndromes.

Chapter 1 provides an overview of frontotemporal lobar degeneration syndromes covered in this thesis. In Chapter 2, I present the experimental methods and techniques used in subsequent experiments. Chapter 3 presents the development of a novel combination of existing methods to detect changes in written text output of an individual with semantic variant of primary progressive aphasia. In Chapter 4, I explored whether a right-sided clinical phenotype, defined according to imaging characteristics, exists for non-fluent variant of primary progressive aphasia. Chapter 5 demonstrates the utility of midbrain-pons ratio and magnetic resonance parkinsonism index in distinguishing different histopathological subtypes found in frontotemporal lobar degeneration syndromes – PSP-tau, CBD-tau and TDP-43 – from the control group, those with Alzheimer’s Disease, and from each other. In Chapter 6, I attempted to examine the prevalence and the nature of sleep disturbance in behavioural variant frontotemporal dementia and how this may differ from those with amnestic Alzheimer’s Disease.