Evidence map›Paper›PMID 26539816›Full record

ArticleAging2015

Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients.

Scott Maynard, Anne-Mette Hejl, Thuan-Son T Dinh, Guido Keijzers, Åse M Hansen, Claus Desler, Maria Moreno-Villanueva, Alexander Bürkle, Lene J Rasmussen, Gunhild Waldemar and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
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

26 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
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  5. Mitochondrial Measures in Primary Cells Isolated from Patients with ME/CFS.Methods in molecular biology (Clifton, N.J.) · 2025
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  19. Mitochondrial dysfunction and increased glycolysis in prodromal and early Parkinson's blood cells.Movement disorders : official journal of the Movement Disorder Society · 2018
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Scott MaynardDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
Anne-Mette HejlDepartment of Neurology, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
Thuan-Son T DinhDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
Guido KeijzersDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
Åse M HansenDepartment of Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Claus DeslerDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
Maria Moreno-VillanuevaMolecular Toxicology Group, University of Konstanz, D-78457 Konstanz, Germany.
Alexander BürkleMolecular Toxicology Group, University of Konstanz, D-78457 Konstanz, Germany.
Lene J RasmussenDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
Gunhild WaldemarDepartment of Neurology, Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
Vilhelm A BohrDepartment of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
University of Copenhagen · DKUniversity of Konstanz · DENational Research Centre for the Working Environment · DKRigshospitalet · DK

Funding

DNA repair dysfunction in neurodegeneration and Alzheimer's DiseaseZIAAG000723 · NIA · NATIONAL INSTITUTE ON AGING · PI BROSH, ROBERT · 2009 to 2025
$9.5M
Processing Of Oxidative Stress In AlzheimerZIAAG000735 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2022
$9.4M
Mitochondrial DNA Repair Processes In Oxidative Stress And AgingZIAAG000733 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2022
$9.2M
Oxidative DNA Damage And Its ProcessingZIAAG000727 · NIA · NATIONAL INSTITUTE ON AGING · PI FERRUCCI, LUIGI · 2009 to 2022
$8.4M
6 · The paper itself

Abstract

aimsAccurate biomarkers for early diagnosis of Alzheimer's disease (AD) are badly needed. Recent reports suggest that dysfunctional mitochondria and DNA damage are associated with AD development. In this report, we measured various cellular parameters, related to mitochondrial bioenergetics and DNA damage, in peripheral blood mononuclear cells (PBMCs) of AD and control participants, for biomarker discovery.

methodsPBMCs were isolated from 53 patients with AD of mild to moderate degree and 30 age-matched healthy controls. Tests were performed on the PBMCs from as many of these participants as possible. We measured glycolysis and mitochondrial respiration fluxes using the Seahorse Bioscience flux analyzer, mitochondrial ROS production using flow cytometry, dNTP levels by way of a DNA polymerization assay, DNA strand breaks using the Fluorometric detection of Alkaline DNA Unwinding (FADU) assay, and APE1 incision activity (in cell lysates) on a DNA substrate containing an AP site (to estimate DNA repair efficiency).

resultsIn the PBMCs of AD patients, we found reduced basal mitochondrial oxygen consumption, reduced proton leak, higher dATP level, and lower AP endonuclease 1 activity, depending on adjustments for gender and/or age.

conclusionsThis study reveals impaired mitochondrial respiration, altered dNTP pools and reduced DNA repair activity in PBMCs of AD patients, thus suggesting that these biochemical activities may be useful as biomarkers for AD.

Indexed as

DNA BreaksAdenosine TriphosphateAgedAge FactorsAlzheimer DiseaseBiomarkersCase-Control StudiesCell RespirationCognitionDNA-(Apurinic or Apyrimidinic Site) LyaseEnergy MetabolismFemaleHumansLeukocytes, MononuclearMaleMiddle AgedAdenosine TriphosphateAPEX1 protein, humanBiomarkersDNA-(Apurinic or Apyrimidinic Site) LyaseNucleotidesAlzheimer's diseaseAPE1bioenergeticsDNA repairdNTP poolsmitochondriaperipheral blood mononuclear cellsreactive oxygen species

Identifiers

PMID26539816
PMCPMC4637207
OpenAlexW2207074962

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.