Evidence map›Paper›PMID 42163007›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Evaluating the causal effect of mitochondrial dysfunction on Alzheimer's disease and Parkinson's disease using polygenic risk scores and Mendelian randomization.

Aadrita Chatterjee, Brian Alvarez, Rakshya U Sharma, Caroline Jonson, Heather M Wilkins, Judy Pa, Russell H Swerdlow, Alison Goate, Kristine Yaffe, Shea J Andrews and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Aadrita ChatterjeeDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0009-0002-6642-6541
Brian AlvarezDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Rakshya U SharmaDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California, USA.
Caroline JonsonCenter for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, Maryland, USA.
Heather M WilkinsDepartment of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Judy PaAlzheimer's Disease Research Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Russell H SwerdlowDepartment of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Alison GoateDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kristine YaffeDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California, USA.
Shea J AndrewsDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0002-1921-9470
Alzheimer's Disease Genetics Consortium and the Alzheimer's Disease Neuroimaging Initiative

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MICHAEL W WEINER · 2016 to 2026
$226.7M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
Project 2 MeasurementU19AG033655 · NIA · JOHNS HOPKINS UNIVERSITY · PI Abhay Moghekar · 2014 to 2026
$51.5M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
National Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Alzheimer's Association 23AARG-1023294Alzheimer's Association AARF-20-675804Alzheimer's Association AG072973Alzheimer's Association R35AG071916Margaret "Peg" McLaughlin and Lydia A. Walker Opportunity FundNational Institute of Neurological Disorders and Stroke (NINDS)NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG086401NIA NIH HHS P30 AG086404NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG006656NIA NIH HHS R01 AG009956NIA NIH HHS R01 AG011101NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG020688NIA NIH HHS R01 AG026916NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG030653NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG041232NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG078186NIA NIH HHS R01 AG079280NIA NIH HHS R35 AG071916NIA NIH HHS R56 AG064877NIA NIH HHS RC2 AG036528NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG054023NIA NIH HHS RF1 AG054074NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG052410NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG033655NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U24 AG072122NIA NIH HHS U54 AG052427NIH HHS R35AG071916NIH HHS ZO1 AG000534NIH-NIA P30AG072973NIH-NIA R01AG078186NINDS NIH HHS R01 NS080820University of Kansas Alzheimer's Disease Center
6 · The paper itself

Abstract

introductionMitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial genomes per nucleated cell, has an unclear causal relationship with Alzheimer's disease (AD) and Parkinson's disease (PD). We integrated genetic correlation, polygenic risk scores (PRSs), and Mendelian randomization (MR) to assess whether mtDNAcn influences the risk of AD and PD, and evaluate how study-specific factors in mtDNAcn genome-wide association studies (GWASs) distort these causal estimates.

methodsUsing GWASs of four mtDNAcn measures, AD, AD/dementia, and PD, we evaluated genetic correlations, generated ancestry-normalized PRS in the Alzheimer's Disease Genetics Consortium (N = 27,383), and applied MR methods including latent heritable confounder-MR (LHC-MR).

resultsAcross the four mtDNAcn GWASs, only one was consistently associated with AD/dementia and PD, with genetic correlations and PRSs showing negative correlations and MR indicating that higher mtDNAcn reduced AD/dementia and PD risk. DISCUSSION: Higher blood-based mtDNAcn was causally associated with reduced risk of AD/dementia and PD, with limited evidence to suggest a bidirectional effect.

Indexed as

Alzheimer DiseaseDNA, MitochondrialMendelian Randomization AnalysisMitochondriaParkinson DiseaseDNA Copy Number VariationsGenetic Predisposition to DiseaseGenetic Risk ScoreGenome-Wide Association StudyHumansMultifactorial InheritanceDNA, MitochondrialAlzheimer's diseasegenetic correlationsMendelian randomizationmitochondrial DNA copy numberParkinson's diseasepolygenic risk scores

Identifiers

PMID42163007
PMCPMC13239222

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.