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

Research output: Contribution to journalJournal articleResearchpeer-review

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Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients. / Maynard, Scott; Hejl, Anne-Mette; Dinh, Tran Thuan Son; Keijzers, Guido; Hansen, Åse M; Madsen, Claus Desler; Moreno-Villanueva, Maria; Bürkle, Alexander; Rasmussen, Lene J; Waldemar, Gunhild; Bohr, Vilhelm A.

In: Aging, Vol. 7, No. 10, 10.2015, p. 793-815.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Maynard, S, Hejl, A-M, Dinh, TTS, Keijzers, G, Hansen, ÅM, Madsen, CD, Moreno-Villanueva, M, Bürkle, A, Rasmussen, LJ, Waldemar, G & Bohr, VA 2015, 'Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients', Aging, vol. 7, no. 10, pp. 793-815.

APA

Maynard, S., Hejl, A-M., Dinh, T. T. S., Keijzers, G., Hansen, Å. M., Madsen, C. D., ... Bohr, V. A. (2015). Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients. Aging, 7(10), 793-815.

Vancouver

Maynard S, Hejl A-M, Dinh TTS, Keijzers G, Hansen ÅM, Madsen CD et al. Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients. Aging. 2015 Oct;7(10):793-815.

Author

Maynard, Scott ; Hejl, Anne-Mette ; Dinh, Tran Thuan Son ; Keijzers, Guido ; Hansen, Åse M ; Madsen, Claus Desler ; Moreno-Villanueva, Maria ; Bürkle, Alexander ; Rasmussen, Lene J ; Waldemar, Gunhild ; Bohr, Vilhelm A. / Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients. In: Aging. 2015 ; Vol. 7, No. 10. pp. 793-815.

Bibtex

@article{b27b39b44d4d43a68a991a4ba3aa4149,
title = "Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients",
abstract = "AIMS: Accurate 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.METHODS: PBMCs 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).RESULTS: In 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.CONCLUSIONS: This 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.",
author = "Scott Maynard and Anne-Mette Hejl and Dinh, {Tran Thuan Son} and Guido Keijzers and Hansen, {{\AA}se M} and Madsen, {Claus Desler} and Maria Moreno-Villanueva and Alexander B{\"u}rkle and Rasmussen, {Lene J} and Gunhild Waldemar and Bohr, {Vilhelm A}",
year = "2015",
month = "10",
language = "English",
volume = "7",
pages = "793--815",
journal = "Aging",
issn = "1945-4589",
publisher = "Impact Journals LLC",
number = "10",

}

RIS

TY - JOUR

T1 - Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients

AU - Maynard, Scott

AU - Hejl, Anne-Mette

AU - Dinh, Tran Thuan Son

AU - Keijzers, Guido

AU - Hansen, Åse M

AU - Madsen, Claus Desler

AU - Moreno-Villanueva, Maria

AU - Bürkle, Alexander

AU - Rasmussen, Lene J

AU - Waldemar, Gunhild

AU - Bohr, Vilhelm A

PY - 2015/10

Y1 - 2015/10

N2 - AIMS: Accurate 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.METHODS: PBMCs 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).RESULTS: In 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.CONCLUSIONS: This 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.

AB - AIMS: Accurate 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.METHODS: PBMCs 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).RESULTS: In 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.CONCLUSIONS: This 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.

M3 - Journal article

VL - 7

SP - 793

EP - 815

JO - Aging

JF - Aging

SN - 1945-4589

IS - 10

ER -

ID: 151493322