Dataset Information

Circulating cell-free mitochondrial DNA levels in Parkinson's disease are influenced by treatment.

ABSTRACT: Several studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer's and Parkinson's disease (PD) patients have raised the hypothesis that ccf-mtDNA could be used as a biomarker for neurodegenerative disease onset and progression. However, how a reduction of CSF ccf-mtDNA levels relates to neurodegeneration remains unclear. Many factors are likely to influence ccf-mtDNA levels, such as concomitant therapeutic treatment and comorbidities. In this study we aimed to investigate these factors, quantifying CSF ccf-mtDNA from the Parkinson's Progression Markers Initiative in 372 PD patients and 159 matched controls at two time points. We found that ccf-mtDNA levels appear significantly reduced in PD cases when compared to matched controls and are associated with cognitive impairment. However, our data indicate that this reduction in ccf-mtDNA is also associated with the commencement, type and duration of treatment. Additionally, we found that ccf-mtDNA levels are associated with comorbidities such as depression and insomnia, however this was only significant if measured in the absence of treatment. We conclude that in PD, similar to reports in HIV and sepsis, comorbidities and treatment can both influence ccf-mtDNA homeostasis, raising the possibility that ccf-mtDNA may be useful as a biomarker for treatment response or the development of secondary phenotypes. Given that, clinically, PD manifests often decades after neurodegeneration begins, predicting who will develop disease is important. Also, identifying patients who will respond to existing treatments or develop secondary phenotypes will have increased clinical importance as PD incidence rises.

SUBMITTER: Lowes H

PROVIDER: S-EPMC7029508 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating cell-free mitochondrial DNA levels in Parkinson's disease are influenced by treatment.

Lowes Hannah H Pyle Angela A Santibanez-Koref Mauro M Hudson Gavin G

Molecular neurodegeneration 20200218 1

Several studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer's and Parkinson's disease (PD) patients have raised the hypothesis that ccf-mtDNA could be used as a biomarker for neurodegenerative disease onset and progression. However, how a reduction of CSF ccf-mtDNA levels relates to neurodegeneration remains unclear. Many factors are likely to influence ccf-mtDNA level ...[more]

PMID: 32070373

Similar Datasets

Project description:ObjectivesThe present study aims to assess the serum circulating cell-free (cfDNA) concentrations in patients with periodontitis and cardiovascular disease (CVD) and to evaluate the impact of periodontitis on circulating cfDNA levels and the confounding factors that might mediated the possible relationship.Materials and methodsHealthy controls (n=30) and patients with CVD (n=31), periodontitis (n=31), and periodontitis + CVD (n=30) were enrolled in the present study. All subjects underwent regular periodontal examination and blood sampling and cfDNA evaluation. The analysis of the plasma cfDNA concentrations was performed using a dsDNA Assay Kit.ResultsIn comparison with healthy controls and CVD patients, periodontitis and periodontitis+CVD exhibited significantly higher expression of circulating cfDNA (p<0.05). There was a positive correlation among plasma cfDNA and clinical attachment loss (CAL) (p=0.019), high sensitivity C-reactive protein (hs-CRP) (p=0.027), and periodontal inflamed surface area (PISA) (p=0.003). Furthermore, the multivariate regression analysis evidenced that PISA (p<0.001), hs-CRP (p=0.014), and full-mouth bleeding score (FMBS) (p=0.004) were significant predictors of circulating cfDNA concentrations.ConclusionsThe results of the study highlighted that the periodontitis and periodontitis + CVD group showed higher circulating cfDNA expression in comparison with healthy controls and CVD patients. Moreover, the extent of periodontitis was correlated with the increased cfDNA levels and represented a significant predictor of the increased circulating cfDNA concentrations.Clinical relevanceUnbalanced circulating cfDNA concentrations have been indicated to represent a possible risk of CVD and endothelial dysfunction. Periodontitis and periodontitis + CVD patients showed higher circulating cfDNA expression; moreover, the extent of periodontitis significantly predicted higher circulating cfDNA concentrations, suggesting the potential increased risk of developing CVD in periodontitis patients.

Project description:BACKGROUND:Adolescent idiopathic scoliosis (AIS) which characterized by complex three-dimensional deformity of spine has been difficult to cure because of the unknown etiopathology and uncertainty of progression. Nowadays, circulating cell-free (ccf) DNA was found to be a potential biomarker for several benign and malignant diseases. However, whether ccf DNA can be a biomarker for AIS has not been reported yet. In this study, we investigate the circulating cell-free nuclear DNA (ccf n-DNA) and mitochondrial DNA (ccf mt-DNA) concentrations in the plasma of patients with AIS and controls (CT), and the changed plasma ccf n-DNA and ccf mt-DNA levels and their association with clinical parameters were assessed. METHODS:The plasma of peripheral blood from 69 AIS patients and 21 age-matched CT was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between the ccf n-DNA and ccf mt-DNA levels and clinical characteristics were conducted. Receiver operator curves (ROC) were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics. RESULTS:The plasma ccf n-DNA levels of both GAPDH and ACTB were significantly decreased in AIS patients compared with those in controls, while the plasma ccf mt-DNA levels did not changed. According to sex-related analyses, the ccf n-DNA levels in male CT-M was higher than that in female CT and male AIS, but the ccf n-DNA levels in female AIS was not significantly changed when compared with male AIS or female CT. However, the concentration of ccf mt-DNA in female AIS increased significantly when compared with male AIS. Surprisingly, Lenke type-related analyses suggested that Lenke type 1 patients had lower ccf n-DNA levels, whereas Lenke type 5 patients had higher ccf mt-DNA levels compared with those of controls. However, a lower sensitivity and specificity of AIS predicted by ccf n-DNA or ccf mt-DNA levels was observed, whether in total, by sex, or by Lenke type. CONCLUSION:Although with no/little predictive accuracy of AIS/progressed AIS by ccf DNA levels, significantly changed plasma ccf DNA levels were observed in AIS patients compared with those in controls.

Dataset Information

Circulating cell-free mitochondrial DNA levels in Parkinson's disease are influenced by treatment.

Publications

Circulating cell-free mitochondrial DNA levels in Parkinson's disease are influenced by treatment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets