{"title":"Elevated serum circulating cell-free mitochondrial DNA in amyotrophic lateral sclerosis.","authors":"Jieyu Li, Chao Gao, Qingqing Wang, Jing Liu, Zhiying Xie, Yawen Zhao, Meng Yu, Yiming Zheng, He Lv, Wei Zhang, Yun Yuan, Lingchao Meng, Jianwen Deng, Zhaoxia Wang","doi":"10.1111/ene.16493","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and purpose: </strong>The substantial role of inflammation in amyotrophic lateral sclerosis (ALS) is gaining support from recent research. Studies indicate that circulating cell-free mitochondrial DNA (ccf-mtDNA) can activate the immune system and is associated with neurodegenerative diseases. This research was designed to quantify ccf-mtDNA levels in the serum of ALS patients.</p><p><strong>Methods: </strong>The medical records of ALS patients were reviewed. Serum ccf-mtDNA levels of patients with ALS (n = 62) and age-matched healthy controls (n = 46) were measured and compared. Additionally, serum interleukin-6 (IL-6) levels were measured using an enzyme-linked immunosorbent assay in 26 ALS patients. Correlations between variables were analyzed.</p><p><strong>Results: </strong>Serum ccf-mtDNA was notably higher in the patients with ALS. When stratified by genotype, the superoxide dismutase 1 (SOD1) mutation group showed the greatest increase in ccf-mtDNA levels relative to other ALS patients. Among all 108 individuals, a cut-off set at 1.1 × 10<sup>5</sup> mtDNA copies on a receiver-operating characteristic curve identified patients with ALS with 80.7% sensitivity and 50.0% specificity; the area under the curve was 0.69 (p < 0.001). Furthermore, serum ccf-mtDNA levels correlated negatively with the progression rate of ALS (ΔFS; rs = -0.26, p = 0.044), but not the ALSFRS-R score (rs = 0.06, p = 0.625). Importantly, the correlation between ccf-mtDNA and ΔFS was more pronounced in the SOD1 mutation group (rs = -0.62, p = 0.018). Lastly, a significant positive association was observed between serum ccf-mtDNA levels and IL-6 levels in ALS (r s= 0.41, p = 0.038).</p><p><strong>Conclusion: </strong>Our study found increased serum ccf-mtDNA in ALS patients, suggesting a link to inflammatory processes and disease mechanism. Moreover, ccf-mtDNA could be an indicator for ALS progression, especially in those with the SOD1 mutation.</p>","PeriodicalId":11954,"journal":{"name":"European Journal of Neurology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/ene.16493","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background and purpose: The substantial role of inflammation in amyotrophic lateral sclerosis (ALS) is gaining support from recent research. Studies indicate that circulating cell-free mitochondrial DNA (ccf-mtDNA) can activate the immune system and is associated with neurodegenerative diseases. This research was designed to quantify ccf-mtDNA levels in the serum of ALS patients.
Methods: The medical records of ALS patients were reviewed. Serum ccf-mtDNA levels of patients with ALS (n = 62) and age-matched healthy controls (n = 46) were measured and compared. Additionally, serum interleukin-6 (IL-6) levels were measured using an enzyme-linked immunosorbent assay in 26 ALS patients. Correlations between variables were analyzed.
Results: Serum ccf-mtDNA was notably higher in the patients with ALS. When stratified by genotype, the superoxide dismutase 1 (SOD1) mutation group showed the greatest increase in ccf-mtDNA levels relative to other ALS patients. Among all 108 individuals, a cut-off set at 1.1 × 105 mtDNA copies on a receiver-operating characteristic curve identified patients with ALS with 80.7% sensitivity and 50.0% specificity; the area under the curve was 0.69 (p < 0.001). Furthermore, serum ccf-mtDNA levels correlated negatively with the progression rate of ALS (ΔFS; rs = -0.26, p = 0.044), but not the ALSFRS-R score (rs = 0.06, p = 0.625). Importantly, the correlation between ccf-mtDNA and ΔFS was more pronounced in the SOD1 mutation group (rs = -0.62, p = 0.018). Lastly, a significant positive association was observed between serum ccf-mtDNA levels and IL-6 levels in ALS (r s= 0.41, p = 0.038).
Conclusion: Our study found increased serum ccf-mtDNA in ALS patients, suggesting a link to inflammatory processes and disease mechanism. Moreover, ccf-mtDNA could be an indicator for ALS progression, especially in those with the SOD1 mutation.
期刊介绍:
The European Journal of Neurology is the official journal of the European Academy of Neurology and covers all areas of clinical and basic research in neurology, including pre-clinical research of immediate translational value for new potential treatments. Emphasis is placed on major diseases of large clinical and socio-economic importance (dementia, stroke, epilepsy, headache, multiple sclerosis, movement disorders, and infectious diseases).