Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

Research output: Contribution to journalJournal articleResearchpeer-review

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

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 languageEnglish
JournalMitochondrion
Volume25
Pages (from-to)34-7
Number of pages4
ISSN1567-7249
DOIs
Publication statusPublished - Nov 2015

ID: 151492789