Blood Mitochondrial DNA Copy Number Is Associated with Motor Symptoms and Dementia in Parkinson’s Disease
Sun Ju Chung1, Sungyang Jo2, Ji-Hye Oh2, Sangjin Lee2, Jihyun Lee2, Chang Ohk Sung2
1Neurology, Asan Medical Center, 2Asan Medical Center
Objective:
We aimed to investigate the association of mitochondrial DNA copy number (mtDNA-CN) obtained from peripheral blood cells with the severity of motor symptoms or cognitive impairment in PD.
Background:
Mitochondria dysfunction affects PD through the accumulation of pathogenic alpha-synuclein, oxidative stress, impaired autophagy, and neuroinflammation. Previous studies showed that blood mtDNA-CN was lower in patients with PD and Alzheimer’s disease than in healthy controls. However, little is known about the correlation between mtDNA-CN and the severity of motor symptoms or dementia in PD.
Design/Methods:
We estimated mtDNA-CN in 405 patients with PD and 200 healthy individuals, using whole genome sequencing for blood samples. We defined mtDNA-CN level as [ 2*mitochondrial DNA coverage/nuclear DNA coverage]. Pearson correlation analysis was performed to find the association between mtDNA-CN and motor severity (UPDRS II+III at medication off state) and Hoehn and Yahr (H&Y) stage. In a subgroup of PD patients who were diagnosed with PD within the last three years, Cox regression analysis was performed to assess the progression of motor symptoms from H&Y stage 2.5 to 3, and the progression to dementia according to mtDNA-CN, after adjusting for age and sex.
Results:
The mtDNA-CN level was significantly lower in patients with PD than in healthy controls (median 179.1 vs. 211.6, P=1.1x10-5). The mtDNA-CN level was negatively correlated with motor severity of PD (r=-0.20; P=0.008). Among 210 patients with early PD within three years from diagnosis, Cox regression analysis showed that patients in the lowest tertile of mtDNA-CN were associated with higher risk of dementia compared to the highest tertile (HR=4.10, CI 1.12−15.26, P=0.03) after adjusting for sex and age. However, mtDNA-CN was not associated with motor progression.
Conclusions:
Our study provides significant association of blood mtDNA-CN with PD and cognitive outcome in PD.