Molecular and Functional Imaging of Parkinson's Pathology in SNCA, Parkin and PINK1 Mutation Carriers

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. The hallmark pathophysiological alteration is a loss of dopaminergic transmission across the nigrostriatal pathway. According to Braak's neuropathological staging of disease, the pathological process in PD occurs in a gradual ascending fashion, starting from the olfactory bulb and progressing to the brainstem, with preferential involvement of the raphe nuclei, which contain serotonergic nuclei, and the noradrenergic locus coeruleus, before involving the substantia nigra and thereafter the whole brain. Little is known about the mechanisms underlying neuronal degeneration in PD and currently, no treatment is available to halt disease progression in PD. The pathophysiological characterisation of phenomena occurring in the time window between the pathological start of the disease and the onset of motor symptoms is crucial to develop potential neuroprotective agents. Several genes causing, the so-called monogenic parkinsonism, have been discovered providing important insights on the pathogenesis of PD.

The objective of the study is to characterize the molecular phenomena underlying genetic forms of parkinsonism and, therefore, providing further insights about the possible mechanisms taking place in PD and help identify targets for disease-modifying therapeutics, by using PET imaging with [11C]DASB (a marker of Serotonin transporter), SPECT imaging using [123I]FP-CIT (a marker of the presynaptic Dopamine transporter), and multi-modal MRI imaging, clinical markers (motor and non-motor symptoms and neuropsychological battery), blood and CSF biomarkers.