Abstract Details

Title Blood Mitochondrial DNA Copy Number Is Associated with Motor Symptoms and Dementia in Parkinson’s Disease

Topic Movement Disorders

Presentation(s) S26 - Movement Disorders: Basic Science (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

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.

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.

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.

Authors/Disclosures
Sun Ju Chung, MD, PhD, FAAN (Neurology, Asan Medical Center) PRESENTER	Dr. Chung has nothing to disclose.
Sungyang Jo, MD (Asan Medical Center)	Dr. Jo has nothing to disclose.
Ji-Hye Oh	No disclosure on file
Sangjin Lee (Asan Medical Center)	No disclosure on file
Jihyun Lee	No disclosure on file
Chang Ohk Sung	No disclosure on file