Qin, P;
Chen, X;
Ma, P;
Li, X;
Lin, Y;
Liu, X;
Liang, X;
... Ouyang, J; + view all
(2025)
Mitochondrial DNA copy number and Alzheimer’s disease and Parkinson disease.
Mitochondrion
, 83
, Article 102032. 10.1016/j.mito.2025.102032.
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Abstract
Introduction: A systematic review on the association of mitochondrial DNA copy number (mtDNA-CN) with Alzheimer's disease (AD) and Parkinson disease (PD) is lacking and the causal relationship remains unclear. Objective: We aimed to conduct a systematic review of observational studies on the association of mtDNA-CN with AD and PD and perform a bidirectional 2-sample Mendelian randomization (MR) study to investigate their causal relationships. Methods: PubMed, Embase, and Web of Science were searched for eligible studies before Jan 2025. The causal links were conducted with inverse-variance weighted (IVW) method as the main analysis. Results: Fourteen case-control and 2 cohort studies investigated the association between mtDNA-CN and AD, with 13 reporting decreased mtDNA-CN associated with increased risk of AD and 3 showing no significant association. All the studies (9 case-control, 1 cross-sectional, 2 cohort studies) observed the relation between mtDNA-CN and PD except for 3 studies reporting no significant association. In MR analysis, genetically predicted mtDNA-CN was not associated with AD and PD, whereas genetically predicted AD (β −0.085, 95 % CI −0.156 to −0.013; P = 0.02) but not PD was associated with mtDNA-CN. Sensitivity and replication analyses showed a stable finding. Discussion: The systematic review found limited observational studies on mtDNA-CN and AD and PD and majority were case-control study. Findings of the bidirectional MR study did not support a causal effect of mtDNA-CN in the development of AD and PD but found that AD can lead to decreased levels of mtDNA-CN, which suggest mtDNA-CN as a potential biomarker of AD.
| Type: | Article |
|---|---|
| Title: | Mitochondrial DNA copy number and Alzheimer’s disease and Parkinson disease |
| Location: | Netherlands |
| DOI: | 10.1016/j.mito.2025.102032 |
| Publisher version: | https://doi.org/10.1016/j.mito.2025.102032 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer’s disease, Mendelian randomization, Mitochondrial DNA copy number, Observational study, Parkinson disease, Systematic review, Humans, Parkinson Disease, Alzheimer Disease, DNA, Mitochondrial, DNA Copy Number Variations, Case-Control Studies, Mendelian Randomization Analysis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Behavioural Science and Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10218862 |
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