Peripheral immune cell abundance differences link blood mitochondrial DNA copy number and Parkinson’s disease

Mitochondrial dysfunction plays an important role in Parkinson’s disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership...

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Bibliographic Details
Published in:NPJ Parkinson's Disease 2024-11, Vol.10 (1), p.219-10, Article 219
Main Authors: Wang, Longfei, Han, Jiru, Fearnley, Liam G., Milton, Michael, Rafehi, Haloom, Reid, Joshua, Gerring, Zachary F., Masaldan, Shashank, Lang, Tali, Speed, Terence P., Bahlo, Melanie
Format: Article
Language:English
Subjects:
631/114/2163
692/53/2421
Biobanks
Biomarkers
Biomedical and Life Sciences
Biomedicine
Blood
Blood platelets
Disease
Estimates
Genetic testing
Genomes
Medical research
Mitochondrial DNA
Neurology
Neurosciences
Parkinson's disease
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Summary:Mitochondrial dysfunction plays an important role in Parkinson’s disease (PD), with mitochondrial DNA copy number (mtDNA-CN) emerging as a potential marker for mitochondrial health. We investigated the links between blood mtDNA-CN and PD severity and risk using the Accelerating Medicines Partnership program for Parkinson’s Disease dataset, replicating our results in the UK Biobank. Our findings reveal that reduced blood mtDNA-CN levels are associated with heightened PD risk and increased severity of motor symptoms and olfactory dysfunction. We estimated blood cell composition using complete blood cell profile when available or RNA-sequencing data as a surrogate. After adjusting for blood cell composition, the associations between mtDNA-CN and PD risk and clinical symptoms became non-significant. Bidirectional Mendelian randomization analysis also found no evidence of a direct causal relationship between blood mtDNA-CN and PD susceptibility. Hence peripheral inflammatory immune responses rather than mitochondrial dysfunction underpin these previously identified associations in PD.
ISSN:2373-8057
2373-8057
DOI:10.1038/s41531-024-00831-x