Abstract
Alzheimer's disease, neurodegenerative disease
ALZHEIMER'S DISEASE, NEURODEGENERATIVE DISEASE
Declining nicotinamide adenine dinucleotide (NADOral nicotinamide riboside (NR) supplementation increased nicotinamide adenine dinucleotide (NAD+) in extracellular vesicles enriched for neuronal origin (NEVs) and decreased biomarkers of neurodegenerative disease and insulin signaling in late middle‐aged and older adults.
These authors share senior and corresponding authorship.Nicotinamide adenine dinucleotide (oxidized form, NADThe brain is particularly vulnerable to alterations in NADWhile the preclinical evidence for the use of NR and other NADNEVs were enriched using an immunoaffinity capture method targeting a sub‐population of plasma EVs that express the neuronal marker L1CAM (described in detail in Mustapic et al. (We measured NADNADThe concentration of Aβ42, p‐Tau‐181, and total Tau in NEVs did not change following NR relative to placebo when analyzing all participants; however, we observed a significant decrease in Aβ42 relative to placebo (Figure NEV biomarkers in response to oral nicotinamide riboside supplementation. (a) Alzheimer's disease biomarkers. (b) Canonical insulin/Akt signaling mediators. (c) Alternative MAPK insulin signaling biomarkers. Two‐tailed paired We hypothesized that the effects of NR on NEV protein biomarkers would be, at least in part, linked to changes in NADIn conclusion, we report the first study examining NEV biomarkers in response to oral NR supplementation. Our primary analysis of NADA mechanism by which NR may alter cellular functions is by increasing NADOur results provide insights into neuronal effects of NR in living humans and highlight the utility of circulating NEVs as a means of demonstrating target engagement in clinical trials. We also show that the utility of NEVs as a source of biomarkers may be expanded beyond proteins to include small molecules, such as NAD