Objective: To identify potential biomarkers for Parkinson’s disease by evaluating miRNA in cerebrospinal fluid samples collected from PD and healthy control subjects.

Background: The diagnosis of Parkinson’s disease (PD) currently relies on clinical recognition of cardinal motor symptoms. Yet the clinical manifestations of PD are highly heterogeneous and the underlying pathophysiologic mechanisms which lead to disease are poorly understood. miRNAs are short, noncoding RNAs that regulate genes, and in the brain their regulatory effects have profound effects on neuronal development (1). Prior studies have shown deregulation of miRNAs in neurodegenerative diseases, including several studies that suggest a role for miRNAs in the pathogenesis of PD (2). We believe that the microRNA (miRNA) profile of PD brains may offer insight into the molecular and pathological mechanisms that occur in the disease and prove to be a useful biomarker for identifying PD patients and clinical subtypes.

Methods: Ten PD patients meeting UK Brain Bank Criteria for the diagnosis of PD and ten healthy control subjects had CSF collected for miRNA analysis. Each subject underwent a clinical assessment and Montreal Cognitive Assessment. miRNA levels were measured using the HTG protocol. Analysis was performed to identify differentially expressed miRNA with a false discovery rate q<0.05.

Results: In this ongoing study, we anticipate identification of a specific profile of miRNA in PD patients compared to healthy controls. Stratification of patients based on MOCA score and clinical symptomatology allows us to identify unique miRNA profiles. We compared our findings with those for miRNAs previously found in studies of PD versus control CSF and post-mortem brain specimens, including miR-132-5p, miR-127-3p, miR-212-3p, and miR-1224-5p.

Conclusions: This pilot study shows whether miRNA can be reliably detected in PD and control CSF samples. It also evaluates the utility of miRNA profiles for identification of patients with PD compared to healthy controls. Future studies looking at larger populations of PD patients and controls will help to classify patient subgroups with clinically similar symptom clusters and, hopefully, yield a reliable biomarker for early detection of PD.

References: 1. O’Carroll, D., and Schaefer, A. (2013). General principals of miRNA biogenesis and regulation in the brain. Neuropsychopharmacology 38, 39-54. 2. Chan, A.W., and Kocerha, J. (2012). The Path to microRNA Therapeutics in Psychiatric and Neurodegenerative Disorders. Front Genet 3, 82.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/micrornas-as-biomarkers-for-parkinsons-disease/