Project - Investigating blood immune biomarkers in prodromal Parkinson's disease patients
Parkinson’s Disease, Prodromal Parkinson’s Disease, idiopathic REM sleep behaviour disorder (iRBD)
Research Project Description
PD is a common, progressive neurodegenerative condition, with more than 30 new cases being diagnosed daily in Australia. The clinical course for many patients with PD is long and slow, often occurring over decades. A strong link has recently been established between diagnosis with iRBD, where patients present with a lack of motor inhibition during sleep, and the subsequent future risk of getting PD. In which, 80% of patients diagnosed with iRBD transition to synucleinopathies, with PD being the most common outcome. Importantly, iRBD can occur up to 15 years prior to the clinical diagnosis of PD, and has been associated with very early peripheral α-synuclein pathology, suggesting that these patients are in a prodromal or pre-clinical phase of PD. For such reasons, there is global interest in developing peripheral biomarkers that allow for early and accurate diagnosis of PD.
Research Project Aims:
- Collect peripheral mononuclear cells and plasma from patients with and without PD, and with idiopathic REM sleep behaviour disorder.
- Measure inflammatory cytokines, immune cell subsets and activation markers in the collected samples.
- Measure leucine-rich repeat kinase 2 (LRRK2), glucocerebrocidase (GBA) and alpha-synuclein in the collected samples.
- Determine the immune cell response to inflammatory agonists across the different groups.
Methodology and work plan:
During the course of this project patients with polysomnography confirmed iRBD, as well as patients with PD and matched controls will be studied. Recruited patients will donate venous blood, which will be used to generate plasma and peripheral blood mononuclear cells.
To determine if peripheral inflammation is increased early in PD pathogenesis, multiplex ELISA methodology techniques will be performed to measure inflammatory cytokines in the serum of the recruited participants. As well as serum cytokines, flow cytometry will be conducted to immunophenotype the participants and to measure GBA activity.
Flow cytometry and ELISA assays will also be used to measure the levels and activity of LRRK2 and its downstream Rab GTPase substrates in monocytes. The immune cell response to inflammatory agonists across the different cohorts will be characterised.
I would like to thank my supervisors Dr. Nicolas Dzamko and Prof. Glenda Halliday for their support during my candidature.