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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

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

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MAYNARD, Scott, Anne-Mette HEJL, Thuan-Son T. DINH, Guido KEIJZERS, Ase M. HANSEN, Claus DESLER, Maria MORENO-VILLANUEVA, Alexander BUERKLE, Lene J. RASMUSSEN, Gunhild WALDEMAR, Vilhelm A. BOHR, 2015. Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients. In: Aging. 7(10), pp. 793-815. eISSN 1945-4589

@article{Maynard2015Defec-33246, title={Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients}, year={2015}, doi={10.18632/aging.100810}, number={10}, volume={7}, journal={Aging}, pages={793--815}, author={Maynard, Scott and Hejl, Anne-Mette and Dinh, Thuan-Son T. and Keijzers, Guido and Hansen, Ase M. and Desler, Claus and Moreno-Villanueva, Maria and Buerkle, Alexander and Rasmussen, Lene J. and Waldemar, Gunhild and Bohr, Vilhelm A.} }

Keijzers, Guido Rasmussen, Lene J. Moreno-Villanueva, Maria Waldemar, Gunhild 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.<br />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).<br />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. 2016-03-07T07:43:25Z Buerkle, Alexander Waldemar, Gunhild Keijzers, Guido Dinh, Thuan-Son T. Defective mitochondrial respiration, altered dNTP pools and reduced AP endonuclease 1 activity in peripheral blood mononuclear cells of Alzheimer's disease patients Bohr, Vilhelm A. Maynard, Scott eng Desler, Claus Hansen, Ase M. Hansen, Ase M. Buerkle, Alexander Dinh, Thuan-Son T. 2016-03-07T07:43:25Z Maynard, Scott Bohr, Vilhelm A. Hejl, Anne-Mette Moreno-Villanueva, Maria Rasmussen, Lene J. 2015 Desler, Claus Hejl, Anne-Mette

Dateiabrufe seit 07.03.2016 (Informationen über die Zugriffsstatistik)

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