Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

TY - JOUR

T1 - Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

AU - Madsen, Claus Desler

AU - Frederiksen, Jane H

AU - Olsen, Maria Nathalie Angleys

AU - Maynard, Scott

AU - Keijzers, Guido

AU - Fagerlund, Birgitte

AU - Mortensen, Erik Lykke

AU - Osler, Merete

AU - Lauritzen, Martin

AU - Bohr, Vilhelm A

AU - Rasmussen, Lene Juel

N1 - Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD.

AB - Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD.

U2 - 10.1016/j.mito.2015.09.002

DO - 10.1016/j.mito.2015.09.002

M3 - Journal article

C2 - 26408413

SN - 1567-7249

VL - 25

SP - 34

EP - 37

JO - Mitochondrion

JF - Mitochondrion

ER -