Novel Insights into Progressive Supranuclear Palsy and Related Disorders

The main aim of this thesis was to assess clinical, neuropathological and neurochemical aspects within this spectrum, but focused mainly on PSP. Furthermore, we describe a mutation in a novel neurodegenerative disorder.

Chapter 1 provides a general overview of PSP, including clinical, genetic and pathological aspects. In chapter 2.1 a comparative study on survival in two large cohorts of PSP and FTD patients is described. The next chapters focus on the clinicoradiological (chapter 2.2) and neurochemical (chapter 3) aspects of the midcingulate cortex in PSP. The latter includes an analysis of twenty different receptors from seven neurotransmitter systems in 16 post-mortem PSP brains. Chapter 4 comprises studies of PSP-like disorders. In chapter 4.1 we describe the various steps to link a mutation to a novel neurodegenerative disorder clinically characterized by dementia and/or parkinsonism. Chapter 4.2 contains the description of neuropathological changes of a presymptomatic carrier of a frontotemporal dementia (FTD) tau mutation, a related hereditary tauopathy. Finally, in the general discussion (chapter 5) the main findings in light of the current knowledge about the disease are discussed and recommendations for future research are made.