Nicotinamide Riboside Reduces Amyloid Plaque Formation and Improves Contextual Memory in Alzheimer's Disease: Preclinical Findings

Synopsis

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder driven by the accumulation of toxic amyloid-β (Aβ) protein aggregates. This study identifies a conserved mitochondrial stress response as a key protective mechanism across humans, mice, and Caenorhabditis elegans models of Aβ toxicity. Through bioinformatic and experimental analyses, researchers found that diseases involving Aβ aggregation share a distinct mitochondrial unfolded protein response (UPRmt) and mitophagy activation pattern—both essential for maintaining mitochondrial proteostasis and cellular health. In a C. elegans model of Aβ proteotoxicity (GMC101), stimulating these mitochondrial quality-control pathways—either genetically or with pharmacological agents, such as nicotinamide riboside—improved mitochondrial function, reduced amyloid accumulation, and extended lifespan. These findings demonstrate that enhancing mitochondrial proteostasis and mitophagy can counteract amyloid-induced cellular stress, offering a promising therapeutic avenue to delay or mitigate Alzheimer’s disease progression.

Journal

Nature