Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

Claus Desler Madsen; Jane H Frederiksen; Maria Nathalie Angleys Olsen; Scott Maynard; Guido Keijzers; Birgitte Fagerlund; Erik Lykke Mortensen; Merete Osler; Martin Lauritzen; Vilhelm A Bohr; Lene Juel Rasmussen

doi:10.1016/j.mito.2015.09.002

Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

Claus Desler Madsen, Jane H Frederiksen, Maria Nathalie Angleys Olsen, Scott Maynard, Guido Keijzers, Birgitte Fagerlund, Erik Lykke Mortensen, Merete Osler, Martin Lauritzen, Vilhelm A Bohr, Lene Juel Rasmussen

Research output: Contribution to journal › Journal article › Research › peer-review

10 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Mitochondrion
Volume	25
Pages (from-to)	34-7
Number of pages	4
ISSN	1567-7249
DOIs	https://doi.org/10.1016/j.mito.2015.09.002
Publication status	Published - Nov 2015

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10.1016/j.mito.2015.09.002

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Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline. / Madsen, Claus Desler; Frederiksen, Jane H; Olsen, Maria Nathalie Angleys; Maynard, Scott; Keijzers, Guido; Fagerlund, Birgitte ; Mortensen, Erik Lykke ; Osler, Merete ; Lauritzen, Martin ; Bohr, Vilhelm A ; Rasmussen, Lene Juel.

In: Mitochondrion, Vol. 25, 11.2015, p. 34-7.

Research output: Contribution to journal › Journal article › Research › peer-review

Madsen, Claus Desler ; Frederiksen, Jane H ; Olsen, Maria Nathalie Angleys ; Maynard, Scott ; Keijzers, Guido ; Fagerlund, Birgitte ; Mortensen, Erik Lykke ; Osler, Merete ; Lauritzen, Martin ; Bohr, Vilhelm A ; Rasmussen, Lene Juel. / Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline. In: Mitochondrion. 2015 ; Vol. 25. pp. 34-7.

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title = "Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline",

abstract = "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.",

author = "Madsen, {Claus Desler} and Frederiksen, {Jane H} and Olsen, {Maria Nathalie Angleys} and Scott Maynard and Guido Keijzers and Birgitte Fagerlund and Mortensen, {Erik Lykke} and Merete Osler and Martin Lauritzen and Bohr, {Vilhelm A} and Rasmussen, {Lene Juel}",

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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

PY - 2015/11

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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.

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DO - 10.1016/j.mito.2015.09.002

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VL - 25

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JO - Mitochondrion

JF - Mitochondrion

SN - 1567-7249

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