Nicotinamide Riboside (NR) for Alzheimer's Disease
Also known as: NR, Niagen, TruNiagen
Brain NAD+ levels decline with aging and AD, contributing to mitochondrial dysfunction and impaired DNA repair.
Mechanism of Action
NR-derived NAD+ activates SIRT1, promoting mitochondrial biogenesis, enhancing autophagic Aβ clearance, and reducing tau acetylation. It supports PARP1-mediated DNA repair stressed by oxidative damage and maintains calcium homeostasis through CD38-dependent signaling.
General mechanism: NAD+ precursor via NR kinase pathway. SIRT1/3 activator, mitochondrial biogenesis enhancer, PARP1 substrate, DNA repair support.
Current Evidence
Preclinical AD models show cognitive improvement with NR supplementation. Human trials for brain NAD+ augmentation ongoing. The NAD+ depletion hypothesis in aging/AD is well-supported.
Clinical Status: Phase II for brain aging. AD-specific trials emerging.
Safety Profile
Very safe at 300-1000mg/day. Mild GI effects. Well-tolerated in clinical trials. No significant drug interactions.
Key Research Questions
- Can NR restore brain NAD+ levels in AD patients measured by MRS?
- Does NR's SIRT1 activation reduce tau pathology in human AD?