Mitochondrial and inflammatory biomarkers in patients with Parkinson's disease and REM sleep behaviour disorder

Abstract

Parkinson’s Disease (PD) pathologically defined by the accumulation of alpha-synuclein (α-syn) aggregates and selective loss of dopaminergic neurons is the most common neurodegenerative movement disorder and one of the world’s fastest-growing neurological disease. The clinical course for many patients with PD is long and slow, often occurring over decades. There are currently no treatments that can slow or stop PD, resulting in a progressively incapacitating disorder that culminates in considerable disability. A lack of simple blood-based biomarkers to diagnose and track the progression of PD is a main contributor to the current lack of treatments. Mitochondrial dysfunction, increased mitochondrial reactive oxygen species (ROS) and inflammation have presented as having significant roles in the progression of PD. The objective of this thesis was to determine if peripheral mitochondrial and inflammatory readouts may comprise as diagnostic and prognostic biomarkers of PD. Mitochondrial measures were conducted on peripheral blood mononuclear cells (PBMCs) and monocytes while inflammatory measures were performed on plasma and serum samples of PD, idiopathic REM sleep behavior disorder (iRBD), and healthy control samples. Initially a flow cytometry assay was optimised and validated using healthy donor PBMCs. The optimised mitochondrial flow assay was utilised to measure differences in mitochondrial parameters between patient and healthy control samples at baseline and at stimulation. The study constituted of 105 subjects in total: 35 healthy controls, 35 iRBD patient and 35 PD patient PBMC samples. The data revealed significant differences in the levels of mitochondrial ROS (p<0.05) and mitochondrial content (p<0.05) in PD samples compared to controls at baseline.