Abstract
Like any organ, the brain is susceptible to the march of time and a reduction in mitochondrial biogenesis is a hallmark of the aging process. In the largest investigation of mitochondrial copy number in Parkinson's disease (PD) to date and by using multiple tissues, we demonstrate that reduced Parkinson DNA (mitochondrial DNA mtDNA) copy number is a biomarker for the etiology of PD. We used established methods of mtDNA quantification to assess the copy number of mtDNA in n = 363 peripheral blood samples, n = 151 substantia nigra pars compacta tissue samples and n = 120 frontal cortex tissue samples from community-based PD cases fulfilling UK-PD Society brain bank criteria for the diagnosis of PD. Accepting technical limitations, our data show that PD patients suffer a significant reduction in mtDNA copy number in both peripheral blood and the vulnerable substantia nigra pars compacta when compared to matched controls. Our study indicates that reduced mtDNA copy number is restricted to the affected brain tissue, but is also reflected in the peripheral blood, suggesting that mtDNA copy number may be a viable diagnostic predictor of PD.
Highlights
Parkinson’s disease (PD) is a prototypical age-related neurodegenerative disease, affecting approximately 1% of the worldwide elderly population
We initially investigated the role of mitochondrial DNA (mtDNA) copy number in peripheral white blood cells (PBCs), identifying a significant reduction in mtDNA copy number in PD cases when compared to controls
We were able to identify a significant association between reduced PBC mtDNA copy number and smoking history in PD cases (Mann-Whitney p 1⁄4 4.0 Â 10À3, Table 1); we found no direct link between smoking history and PD
Summary
Parkinson’s disease (PD) is a prototypical age-related neurodegenerative disease, affecting approximately 1% of the worldwide elderly population. The etiopathogenesis of PD is complex and multifactorial, including contributions from environmental and genetic factors, with aging remaining the strongest risk factor. Subsequent studies, focusing on complex I-mediated reactive oxygen species formation link PD to a vicious circle of oxidative stress and bioenergetic failure. At the cellular genetic level, reports have indicated that mitochondrial DNA (mtDNA) deletion formation may contribute to etiology (Reeve et al, 2013); these isolated findings cannot fully explain the gross neuronal loss seen in PD. Comprehensive population studies, focusing on the role of inherited mtDNA variants, have identified phylogenetic clades which reproducibly affect PD risk (Ghezzi et al, 2005; Hudson et al, 2013, 2014; Latsoudis et al, 2008)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
