Circulating miRNAs as Diagnostic Biomarkers for Parkinson's Disease

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Its main neuropathological hallmarks are the degeneration of dopaminergic neurons in the substantia nigra and alpha-synuclein containing protein inclusions, called Lewy Bodies. The diagnosis of idiopathic PD is still based on the assessment of clinical criteria, leading to an insufficient diagnostic accuracy. Additionally, there is no biomarker available allowing the prediction of the disease course or monitoring the response to therapeutic approaches. So far, protein biomarker candidates such as alpha-synuclein have failed to improve diagnosis of PD. Circulating microRNAs (miRNAs) in body fluids are promising biomarker candidates for PD, as they are easily accessible by non- or minimally-invasive procedures and changes in their expression are associated with pathophysiological processes relevant for PD. Advances in miRNA analysis methods resulted in numerous recent publications on miRNAs as putative biomarkers. Here, we discuss the applicability of different body fluids as sources for miRNA biomarkers, highlight technical aspects of miRNA analysis and give an overview on published studies investigating circulating miRNAs as biomarker candidates for diagnosis of PD and other Parkinsonian syndromes.

Keywords: CSF; Parkinsonian syndromes; Parkinson’s disease; biomarker; blood; miRNA; neurodegeneration.

FIGURE 1

Circulating miRNAs as biomarkers for PD and other Parkinsonian syndromes. (A) Methodological aspects to consider in circulating biomarker research. (B) Proportion of the human miRNAome demonstrated to be significantly regulated in biomarker studies for PD and other Parkinsonian syndromes.

FIGURE 2

Differentially regulated miRNAs ranked according to strength of the study. Each bar represents one individual study, where the miRNA(s) indicated in the middle column was identified differentially regulated. miRNA names are set bold when appearing in more than one study. Length of the bars correspond to the number of subjects in the study cohort (patients + controls). Color of the bars represents significant down- (blue) or up-regulation (red) in miRNA expression in respect to the PD group. Color intensity indicates strength of the study by considering the number of centers for sample recruitment and existence of a validation cohort per study (full color: multicentric study with validation cohort; 75% color: monocentric study with validation cohort; 50% color: multicentric study without validation cohort; 25% color: monocentric study without validation cohort). Bars are patterned according to the biological source used in each study (horizontally striped: whole blood; solid: plasma or serum; dotted: PBMCs; vertically striped: CSF). ^∗ = studies where results were acquired or confirmed using qRT-PCR.