**Boosting NAD⁺ Shows Promise in Protecting the Brain from Alzheimer’s Disease Degeneration**
*Published on Medical Xpress | University of Oslo | Science Advances — November 10, 2025*
*By Ruixue Ai et al*
Alzheimer’s disease (AD), the leading cause of dementia worldwide, affects nearly 40 million individuals. Despite decades of extensive research, no treatments have yet been found that can halt or reverse the progression of this devastating disease.
A major contributor to neuronal dysfunction in AD is the protein tau. Now, an international team of researchers has uncovered a new mechanism by which boosting the natural metabolite NAD⁺ can protect the brain from AD-related degeneration.
### What is NAD⁺?
NAD⁺ (nicotinamide adenine dinucleotide, oxidized form) is a vital metabolite involved in energy metabolism and neuronal resilience. Levels of NAD⁺ naturally decline with age and more markedly in various neurodegenerative diseases, including AD.
Preliminary studies have demonstrated that supplementation with NAD⁺ precursors, such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), may provide therapeutic benefits in AD animal models and early-stage clinical trials.
### New Mechanism Discovered: NAD⁺ and RNA Splicing
The new study reveals that NAD⁺ operates through a previously unidentified RNA-splicing pathway regulated by a protein called EVA1C. RNA splicing is a crucial process where the components of RNA are correctly assembled to form functional genes.
Dysregulation of RNA splicing is one of the most recently recognized risk factors for Alzheimer’s disease. The researchers found that increasing NAD⁺ levels enhances EVA1C activity, which in turn helps correct errors in RNA splicing. This correction improves the function of hundreds of genes, many of which are vital for brain health, potentially reversing neurodegenerative damage caused by tau protein.
Further analysis showed that NAD⁺ promotes a specific form of EVA1C that efficiently binds to key proteins essential for proper protein folding and clearance. This discovery links three critical biological processes—metabolic homeostasis, RNA splicing, and protein management—that are severely impaired in AD.
### Implications for Alzheimer’s Treatments
“We propose that maintaining NAD⁺ levels could help preserve neuronal identity and delay cognitive decline,” says Ruixue Ai. She adds, “This opens up new possibilities for combination therapies that enhance RNA splicing alongside NAD⁺ supplementation.”
These findings mark an important step towards understanding how metabolic interventions might slow or reverse Alzheimer’s progression and improve brain resilience.
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**Read more on Medical Xpress:** [medicalxpress.com](https://medicalxpress.com)
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**About the Author:**
Ruixue Ai and colleagues are part of an international research team dedicated to uncovering the molecular mechanisms behind Alzheimer’s disease and exploring novel therapeutic approaches.
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