Abstract
BACKGROUND: MicroRNA-7-5p (miR-7-5p) may play a neuroprotective role in people with Parkinson's disease (PwP), as it has been found to regulate α-synuclein (α-syn) and the NLRP3 inflammasome in animal models of Parkinson's disease (PD). OBJECTIVE: The study aimed to investigate the use of miR-7-5p as a potential biomarker for disease progression in PwP by correlating it with time, clinical measures, and neurofilament light chain (NfL). METHODS: We performed a longitudinal retrospective analysis of blood miR-7-5p levels in 303 de novo PwP and 159 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort. In PwP, a linear mixed-effects model was used to examine the association between miR-7-5p levels and time in the study. In addition, linear mixed-effects models were used to examine the associations between longitudinal changes in miR-7-5p and scores on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), both for motor and total scores, as well as serum NfL levels. These models were also used to compare the associations between changes in miR-7-5p, time in the study, and NfL levels in both PwP and HCs. RESULTS: miR-7-5p levels decreased more rapidly in PwP compared to HCs (p = 0.02). In PwP, miR-7-5p levels correlated with time in the study (p < 0.001) and with changes in the MDS-UPDRS motor (p = 0.007) and total scores (p = 0.01). However, when time in study was taken into account, the correlations were no longer significant. Additionally, miR-7-5p levels decreased longitudinally as NfL levels increased in PwP (p = 0.03), but this did not remain significant when time in the study was considered. CONCLUSION: This pattern suggests that miR-7-5p may reflect both upstream pathogenic mechanisms and downstream neuroaxonal damage. However, the loss of significance when time in the study was included in the model indicates that the changes may reflect parallel degenerative processes involving NfL and miR-7-5p. This study is novel in that it demonstrates a correlation between miR-7-5p levels, clinical severity, and NfL levels.