Blood-Based Biomarkers Diagnose Parkinson's Disease

Objective and measurable biomarkers to improve Parkinson's Disease (PD) diagnostics would be advantageous during its earlier stage, prior to the motor onset phase.

Blood-based circulating micro ribonucleic acid (miRNA) biomarkers for PD are quantifiable, as it is known that miRNAs detected in various cells and tissues can also be found in biofluids such as blood plasma and serum.

Scientists at the Van Andel Institute (Grand Rapids, MI, USA) obtained the global miRNA expressions in plasma from an initial discovery set of 32 PD patients and 32 normal controls. They identified nine pairs of PD-predictive classifiers and 13 most differentially expressed miRNAs as potential biomarkers to discriminate PD patients from normal controls.

The team used a quantitative real-time polymerase chain reaction technique (qRT-PCR) to validate and evaluate the performance of these biomarkers. The study subjects were all recruited between January 2006 and November 2009. Total RNA that included miRNAs was isolated from plasma using the TRI reagent RT-blood protocol (Molecular Research Center, Cincinnati, OH, USA). RNA samples were processed, labeled, and hybridized onto microarrays.

The investigators identified nine pairs of PD-predictive classifiers and 13 most-differentially expressed miRNAs as potential biomarkers to discriminate PD patients from normal controls. The combination of biomarkers that achieved the highest predictive performance was applied to another set of 42 PD patients and 30 controls from the same clinical site. A new, independent validation set of samples from 30 PD patients from a different clinical site showed lower biomarker performance.

Sok Kean Khoo, PhD, the senior author said, “The ideal biomarker should be minimally invasive, cost efficient, quantifiable, reproducible, specific, and sensitive. Biofluids such as plasma could provide an ideal resource for development of such desirable biomarkers. This is a proof-of-concept study to demonstrate the feasibility of using plasma-based circulating miRNAs. The hypothesis that miRNA expression changes are associated with the neurodegenerative disease process, either directly or as part of positive feedback loops, is emerging rapidly. This study opens new opportunities to the exploration of circulating miRNAs for diagnostic, prognostic, and therapeutic interventions for PD and possibly other neurodegenerative diseases.” The study was published in the December 2012 issue of the Journal of Parkinson's Disease.

Related Links:
Van Andel Institute
Molecular Research Center