Abstract
Recent work has shown loss of phosphodiesterase 10A (PDE10A) expression in middle-stage and advanced treated patients with Parkinson’s disease, which was associated with motor symptom severity. In this thesis, I used molecular imaging to evaluate whether the reduction of PDE10A expression is characteristic of the early stages of the Parkinson’s disease and is related to disease severity and other markers of Parkinson’s disease pathology via the following objectives:1) By using [11C]IMA107 PET imaging to assess the integrity of PDE10A enzyme in vivo in early de
novo and early levodopa-treated patients with Parkinson’s disease compared to age- and sex-matched healthy control subjects (Project 1)
2) Compare and investigate the associations between the expression of PDE10A with known molecular markers of dopaminergic dysfunction in Parkinson’s patients such as loss of dopamine transporters, as quantified with [11C]PE2I PET and [123I]FP-CIT SPECT molecular imaging (Project 2)
3) Explore the associations between the expression of PDE10A with MRI markers of Parkinson’s pathology such as iron depositions (assessed with susceptibility-weighted MR imaging), neuromelanin loss (assessed with neuromelanin sensitive MR imaging) and changes in structural volumetric (assessed with T1 MR imaging) and connectivity (assessed with diffusion tensor MR imaging) (Project 3)
4) Investigate for associations between the expression of PDE10A and non-motor symptoms considered pre-motor (sleep problems, autonomic dysfunction, mood disorders etc).
Overall, the findings of this thesis indicate that loss of PDE10A expression is a very early phenomenon during Parkinson’s disease and is associated with the disease duration and gradual increase of motor symptom burden in different disease stages. PDE10A PET was not associated with non-motor symptoms. PDE10A PET shows a diagnostic power similar to DAT PET and DAT SPECT, but greater than any MRI imaging modalities. This suggests PDE10A imaging as a robust alternative worth exploring further for use in clinical practice.
| Date of Award | 2019 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Mitul Mehta (Supervisor) & Marios Politis (Supervisor) |