Identifying the potential role of serum miR-20a as a biomarker for olfactory dysfunction in patients with Parkinson's disease.

Abstract

Olfactory dysfunction (OD), one of the most common non-motor symptoms in Parkinson's disease (PD), is a cardinal prodromal symptom that can appear years before the onset of motor symptoms. Ongoing studies have demonstrated that microRNAs (miRNAs) are suitable biomarkers for PD, while there is a lack of robust miRNAs that can serve as markers for OD in PD. The concordantly differentially expressed miRNAs (DE miRNAs) in the damaged olfactory system were first identified in 2 OD-related Gene Expression Omnibus (GEO) datasets. Then, they were verified in another PD-related GEO dataset and only one miRNA (miR-20a) was found to be significantly altered. Serum levels of miR-20a were further measured by qPCR in 79 PD patients with OD (PD-OD), 52 PD patients without OD (PD-NOD), and 52 healthy controls (HC). Objective measure of OD was defined by 16-item Sniffin' Sticks odor identification test. All the participants underwent a demographic and comprehensive PD-related clinical assessment. Our results proved that miR-20a was significantly downregulated in PD-OD compared with PD-NOD and the area under curve (AUC) for OD detection by miR-20a was 0.803 (95% confidence interval, 0.724-0.883). In addition, PD-OD had higher scores of Movement Disorder Society-Unified Parkinson's Disease Rating Scale (UPDRS) II, Hoehn and Yahr stage (H-Y), Non-Motor Symptoms Scale (NMSS) 3, NMSS 5, NMSS 9, Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), Activity of Daily Living (ADL), and lower scores of Mini-Mental State Examination (MMSE) and 39-item PD Quality of Life Questionnaire (PDQ-39) than PD-NOD. Binary regression model further presented that lower expressions of miR-20a and poorer cognitive function acted as promoting factors in the development of OD. Our results suggest that miR-20a could be a novel biomarker for OD in PD and PD-OD patients tend to have higher disease stage, poorer motor aspects of experiences of daily living, worse cognitive scores, and inferior quality of life, and were more likely to have mental disorders. Cognitive function, in particular, is strongly associated with OD in PD patients.