Mitochondrial DNA copy number and Alzheimer’s disease and Parkinson disease

IF 3.9 3区生物学 Q2 CELL BIOLOGY

Mitochondrion Pub Date : 2025-03-27 DOI:10.1016/j.mito.2025.102032

Pei Qin , Xiaojuan Chen , Panpan Ma , Xinying Li , Yunying Lin , Xiaoning Liu , Xiaoyan Liang , Tianhang Qin , Junyan Liang , Jipeng Ouyang

{"title":"Mitochondrial DNA copy number and Alzheimer’s disease and Parkinson disease","authors":"Pei Qin , Xiaojuan Chen , Panpan Ma , Xinying Li , Yunying Lin , Xiaoning Liu , Xiaoyan Liang , Tianhang Qin , Junyan Liang , Jipeng Ouyang","doi":"10.1016/j.mito.2025.102032","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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; <em>P</em> = 0.02) but not PD was associated with mtDNA-CN. Sensitivity and replication analyses showed a stable finding.</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":18606,"journal":{"name":"Mitochondrion","volume":"83 ","pages":"Article 102032"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Mitochondrion","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567724925000297","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Mitochondrion 生物-细胞生物学

CiteScore

9.40

自引率

4.50%

发文量

审稿时长

13.6 weeks

期刊介绍： Mitochondrion is a definitive, high profile, peer-reviewed international research journal. The scope of Mitochondrion is broad, reporting on basic science of mitochondria from all organisms and from basic research to pathology and clinical aspects of mitochondrial diseases. The journal welcomes original contributions from investigators working in diverse sub-disciplines such as evolution, biophysics, biochemistry, molecular and cell biology, genetics, pharmacology, toxicology, forensic science, programmed cell death, aging, cancer and clinical features of mitochondrial diseases.