Molecular Pathology and Neuronal Networks in LRRK2 Parkinson's Disease

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically by bradykinesia, resting tremor, rigidity, and postural instability. 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 have been discovered providing important insights on the pathogenesis of PD. Mutations of Leucine-rich repeat kinase 2 (LRRK2) are associated with 2-5% of all PD cases in North American Caucasians. LRRK2 is an enzyme that in humans is encoded by the autosomal dominant Parkinson's disease-8 (PARK8) gene, which is associated with an increased risk of PD. Clinical and digital biomarkers, blood and cerebrospinal fluid (CSF) biomarkers and molecular positron emission tomography (PET) imaging, with specific radioligands, provide invaluable insights to help understand and characterise disease pathophysiology. The investigators aim to characterize molecular phenomena underlying LRRK2 PD with the hope of providing further insights into possible mechanisms taking place in PD and to help identify targets for disease-modifying therapeutics.