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.
authors.affiliation: Center for Healthy Aging, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Desler
authors.affiliation: Center for Healthy Aging, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Jane H
authors.initials: JH
authors.lastname: Frederiksen
authors.affiliation: Center for Healthy Aging, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Angleys
authors.affiliation: Center for Healthy Aging, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Scott
authors.initials: S
authors.lastname: Maynard
authors.affiliation: Center for Healthy Aging, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Guido
authors.initials: G
authors.lastname: Keijzers
authors.affiliation: Center for Healthy Aging, Denmark; Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Centre Glostrup, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Fagerlund
authors.affiliation: Center for Healthy Aging, Denmark; Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Erik Lykke
authors.initials: EL
authors.lastname: Mortensen
authors.affiliation: Department of Public Health, University of Copenhagen, Denmark; Research Center for Prevention and Health, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Osler
authors.affiliation: Center for Healthy Aging, Denmark; Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen N, Denmark; Department of Clinical Neurophysiology, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
authors.affiliation: Center for Healthy Aging, Denmark; Laboratory of Molecular Gerontology, National Institutes on Aging, NIH, United States.
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
authors.affiliation: Center for Healthy Aging, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark. Electronic address: lenera@sund.ku.dk.
authors.forename: Lene Juel
authors.initials: LJ
authors.lastname: Rasmussen
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D015331:Cohort Studies; D004734:Energy Metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis*; D013942:Thymine Nucleotides / Q000032:analysis*
chemical_list: D017382:Reactive Oxygen Species; D013942:Thymine Nucleotides; C024157:thymidine 5'-triphosphate
keywords: Alzheimer's disease; Cognitive decline; Deoxyribonucleotide levels; Mitochondrial ROS; Mitochondrial bioenergetics