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Sex-Independent Upregulation of miR-146a-5p in Parkinson's Disease Patients: A Longitudinal Study
Annamaria Vallelunga1, Tommaso Iannitti2, Giovanna Dati3
1Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, AP 62, Tlaxcala CP 90000, Mexico.
Abstract:
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The absence of reliable fluid biomarkers continues to hinder early diagnosis and effective monitoring of disease progression. Circulating microRNAs (cmiRNAs) are potential candidates, given their stability in biofluids and their ability to mirror pathological processes. We conducted a longitudinal study in 30 early-stage levodopa-naive PD patients (22 men, 8 women). Serum samples were collected at baseline (T0) and at a follow-up time point two years later (T2). A panel of MicroRNAs (miRNAs) (miR-146a-5p, miR-34a-5p, miR-155-5p, miR-29a-3p, miR-106a-5p) were quantified by quantitative real-time PCR. Data were expressed as relative expression (2^-ΔCt), and statistical analyses included sex-stratified comparisons and paired tests for longitudinal changes. At baseline, no significant differences were found in the expression of the miRNAs between male and female PD patients. In contrast, longitudinal within-subject analysis revealed a highly significant upregulation in miR-146a-5p expression from T0 to T2 in both sexes (p < 0.0001). No other miRNAs in the panel exhibited significant changes over time. CmiR-146a-5p levels rise markedly over time in PD patients, independent of sex, suggesting that this miRNA could be a dynamic biomarker of disease progression.
Insights
Circulating microRNAs (cmiRNAs) show promise as biomarkers for Parkinson's disease (PD). In this study, miR-146a-5p levels significantly increased over two years in PD patients, suggesting its potential as a dynamic biomarker for disease progression.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Parkinson's disease (PD) is a progressive neurodegenerative disorder with significant motor and non-motor symptoms.
- Current diagnostic and monitoring methods for PD are limited by the lack of reliable fluid biomarkers.
- Circulating microRNAs (cmiRNAs) are stable in biofluids and may reflect pathological changes, making them potential biomarkers.
Purpose of the Study:
- To investigate the longitudinal changes in specific circulating microRNAs (cmiRNAs) in early-stage, levodopa-naive Parkinson's disease (PD) patients.
- To assess the potential of cmiRNAs as dynamic biomarkers for monitoring PD progression.
- To determine if miRNA expression differs between sexes in PD patients over time.
Main Methods:
- A longitudinal study involving 30 early-stage PD patients (levodopa-naive).
- Serum samples were collected at baseline (T0) and after two years (T2).
- Quantitative real-time PCR was used to measure the expression of five selected miRNAs (miR-146a-5p, miR-34a-5p, miR-155-5p, miR-29a-3p, miR-106a-5p).
Main Results:
- No significant differences in miRNA expression were observed between male and female PD patients at baseline.
- A highly significant upregulation of miR-146a-5p was detected within individuals from T0 to T2 (p < 0.0001), irrespective of sex.
- None of the other assessed miRNAs showed significant longitudinal changes.
Conclusions:
- Circulating miR-146a-5p levels increase markedly over time in Parkinson's disease patients.
- This longitudinal increase is independent of sex, highlighting its potential as a dynamic biomarker for PD progression.
- miR-146a-5p warrants further investigation as a valuable tool for early diagnosis and monitoring of Parkinson's disease.
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