Nicotinamide Riboside Improves Alzheimer's Features and DNA Repair: Preclinical Findings

Synopsis

Alzheimer’s disease (AD) involves problems with energy metabolism and DNA repair, but how these contribute to key AD features is unclear. A DNA repair-deficient AD mouse model (3xTgAD/Polβ+/−) shows worsened Tau protein pathology, synaptic problems, neuron death, and cognitive decline. These mice have a lower brain NAD+/NADH ratio, indicating impaired energy metabolism, which is restored by nicotinamide riboside (NR) treatment. NR reduced Tau pathology, DNA damage, neuroinflammation, and neuron death, while increasing brain SIRT3 activity. It also improved cognition and synaptic plasticity in both AD models, especially the repair-deficient one. These results highlight that NAD+ depletion contributes to AD pathology and that boosting NAD+ in neurons could be a promising therapeutic strategy.

Journal

Proceedings of the National Academy of Sciences