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

Autor: Wang L; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Han J; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Fearnley LG; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Milton M; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Rafehi H; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Reid J; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Epilepsy Research Centre, Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, VIC, Australia., Gerring ZF; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Masaldan S; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Ubiquitin Signalling Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Lang T; Clinical Discovery and Translation, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia., Speed TP; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC, Australia., Bahlo M; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. bahlo@wehi.edu.au.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. bahlo@wehi.edu.au.
Jazyk: angličtina
Zdroj: NPJ Parkinson's disease [NPJ Parkinsons Dis] 2024 Nov 14; Vol. 10 (1), pp. 219. Date of Electronic Publication: 2024 Nov 14.
DOI: 10.1038/s41531-024-00831-x
Abstrakt: 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.
Competing Interests: Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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