Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin

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Author(s)Vreones, Michael
Author(s)Mustapic, Maja
Author(s)Moaddel, Ruin
Author(s)Pucha, Krishna A.
Author(s)Lovett, Jacqueline
Author(s)Seals, Douglas R.
Author(s)Kapogiannis, Dimitrios
Author(s)Martens, Christopher R.
Date Accessioned2023-02-17T19:57:19Z
Date Available2023-02-17T19:57:19Z
Publication Date2023-01-12
DescriptionThis article was originally published in Aging Cell. The version of record is available at: https://doi.org/10.1111/acel.13754
AbstractDeclining nicotinamide adenine dinucleotide (NAD+) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging-associated neurological disorders. Experimental therapies aimed at boosting brain NAD+ levels normalize several neurodegenerative phenotypes in animal models, motivating their clinical translation. Dietary intake of NAD+ precursors, such as nicotinamide riboside (NR), is a safe and effective avenue for augmenting NAD+ levels in peripheral tissues in humans, yet evidence supporting their ability to raise NAD+ levels in the brain or engage neurodegenerative disease pathways is lacking. Here, we studied biomarkers in plasma extracellular vesicles enriched for neuronal origin (NEVs) from 22 healthy older adults who participated in a randomized, placebo-controlled crossover trial (NCT02921659) of oral NR supplementation (500 mg, 2x /day, 6 weeks). We demonstrate that oral NR supplementation increases NAD+ levels in NEVs and decreases NEV levels of Aβ42, pJNK, and pERK1/2 (kinases involved in insulin resistance and neuroinflammatory pathways). In addition, changes in NAD(H) correlated with changes in canonical insulin–Akt signaling proteins and changes in pERK1/2 and pJNK. These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans. Furthermore, NEVs offer a new blood-based window into monitoring the physiologic response of NR in the brain.
SponsorThis work was supported in part by NIH grant K01 AG054731 and in part by the Intramural Program of the National Institute on Aging, NIH. The original clinical trial for which the samples in this study were derived was registered on clinicaltrials.gov under the identifier NCT02921659 and was supported by NIH grants T32 AG000279 and UL1 TR001082 and a fellowship from the Glenn Foundation and American Federation of Aging Research. NR and placebo capsules for the original clinical trial were provided by ChromaDex, Inc.
CitationVreones, M., Mustapic, M., Moaddel, R., Pucha, K. A., Lovett, J., Seals, D. R., Kapogiannis, D., & Martens, C. R. (2023). Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin. Aging Cell, 22, e13754. https://doi.org/10.1111/acel.13754
ISSN1474-9726
URLhttps://udspace.udel.edu/handle/19716/32321
Languageen_US
PublisherAging Cell
Keywordsextracellular vesicles
KeywordsNAD+
KeywordsNADH
Keywordsneurodegenerative disease
TitleOral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin
TypeArticle
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