microRNA expression in the plasma of participants with Parkinson's disease
Parkinson’s disease (PD) is a progressive neurological disorder that affects 1% of the population over the age of 60. The diagnosis of Parkinson’s disease is based on the cardinal feature of bradykinesia along with two of these three: tremor, stiffness or postural instability. Despite this, as many as 20% of patients may be misdiagnosed with a PD mimic.Currently the treatment of PD is purely symptomatic and does not affect the rate of disease progression. Future trials of disease modifying drugs will, ideally, want to identify those with an early stage of disease and to potentially exclude PD mimics, yet there is no reliable way to do this currently.The neurodegenerative process in PD affects more than the dopaminergic neurons associated with movement and the extent of non-motor symptoms are becoming clearer, with the onset of PD associated with depression, anxiety altered sleep and cognitive impairment.We recruited a cohort of 51 patients with a clinical diagnosis of PD. Eleven males with shorter disease durations were selected for a pilot study with eleven age and sex matched controls. All participants were clinically described using several validated questionnaires and had a fasted morning blood sample from which RNA was extracted and analysed on a custom miRNA array card.We found that the incidence of non-motor symptoms was broadly similar in frequency to other cohorts described in the literature. Analysis of miRNA expression found ten differentially expressed miRNA which when paired separated the PD pilot group from their controls with a sensitivity of 100% and a specificity of 81.82%, or a sensitivity of 90.91% and specificity of 100%, depending on the pairing.Bioinformatic analysis of the differentially expressed miRNA suggested they may be important in a number of pathways related to DNA and RNA pathways, signalling pathways and inflammatory pathways.In summary, this initial cohort and small pilot study have shown that participants with PD in the Otago region share many of the non-motor symptoms of PD described in the literature. miRNA analysis has also shown that pairs of differentially expressed miRNA can separate those with a clinical diagnosis of PD from those without with a high degree of certainty.
Advisor: Williams, Joanna; Cutfield, Nick
Degree Name: Master of Medical Science
Degree Discipline: Department of medicine
Publisher: University of Otago
Keywords: Parkinson's disease; miRNA; plasma; cohort; New Zealand; Otago; Diagnosis; signalling pathways; inflammatory pathways
Research Type: Thesis