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

Lookup NU author(s): Dr Hannah Lowes, Dr Angela Pyle, Dr Mauro Santibanez Koref, Dr Gavin Hudson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 The Author(s).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.


Publication metadata

Author(s): Lowes H, Pyle A, Santibanez-Koref M, Hudson G

Publication type: Article

Publication status: Published

Journal: Molecular Neurodegeneration

Year: 2020

Volume: 15

Issue: 1

Online publication date: 18/02/2020

Acceptance date: 13/02/2020

Date deposited: 09/03/2020

ISSN (electronic): 1750-1326

Publisher: BioMed Central Ltd.

URL: https://doi.org/10.1186/s13024-020-00362-y

DOI: 10.1186/s13024-020-00362-y

PubMed id: 32070373


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