NMN Shows Promise Against Alzheimer's Disease

The hunt for effective treatments for Alzheimer's disease has seen countless disappointments over the decades. But emerging research on NAD+ boosting compounds is offering new hope in this challenging field, with Nicotinamide Mononucleotide (NMN) showing particularly promising results.

While we've previously explored NMN's benefits for physical performance and aging, exciting research is uncovering its potential to protect our brains against the devastating effects of Alzheimer's disease.

A Groundbreaking Study

Researchers at Kanazawa University in Japan conducted a fascinating study examining whether NMN could protect against the neurotoxic effects of amyloid-beta oligomers - the primary culprits behind the neuronal damage in Alzheimer's disease.

The researchers didn't just look at cells in test tubes. They used both organotypic hippocampal slice cultures (essentially pieces of actual hippocampus kept alive in lab conditions) and live rats with an Alzheimer's-like condition induced by infusing amyloid-beta oligomers directly into their brains.

This comprehensive approach allowed them to observe NMN's effects from multiple angles - from cellular mechanisms to actual behavioural improvements.

The Protocol

The researchers administered NMN (500 mg/kg) through intraperitoneal injection to the Alzheimer's model rats. This might sound like a high dose, but it's comparable to doses used in other NMN studies that have demonstrated safety.

To test whether the NMN treatment improved cognitive function, they put the rats through the Morris water maze - a classic test of spatial learning and memory where rats must remember the location of a hidden platform in a pool of water.

At the cellular level, they examined whether NMN could prevent the amyloid-beta oligomers from inhibiting long-term potentiation (LTP) - the cellular mechanism that underlies learning and memory.

The Results Were Remarkable

The NMN-treated rats showed significantly better performance in spatial learning and memory tasks compared to the untreated Alzheimer's model rats. In fact, their performance was much closer to that of healthy controls.

At the cellular level, NMN prevented the amyloid-beta oligomers from inhibiting long-term potentiation, suggesting it was protecting the fundamental cellular mechanisms of memory formation.

Perhaps most impressively, NMN attenuated neuronal death caused by the amyloid-beta oligomers. In Alzheimer's disease, neuron loss is progressive and irreversible, so preventing this cell death is crucial.

How Does NMN Work Its Magic?

The researchers didn't just observe these benefits - they dug deeper to understand the mechanisms. What they found gives us valuable insight into how NMN might help combat Alzheimer's disease:

1. Energy Metabolism Restoration: NMN replenished the NAD+ and ATP levels that were depleted by amyloid-beta oligomers. This is crucial because brain cells have enormous energy demands, and energy failure is a key feature of neurodegenerative diseases.

2. Oxidative Stress Reduction: NMN eliminated the buildup of reactive oxygen species (ROS) that occurred in response to amyloid-beta oligomers. Oxidative stress is a major contributor to brain aging and neurodegeneration.

3. Neuronal Protection: By supporting energy production and reducing oxidative damage, NMN created conditions where neurons could survive despite the presence of toxic amyloid-beta oligomers.

To confirm that these benefits were specifically due to NMN's effect on NAD+ metabolism, the researchers used a compound called 3-acetylpyridine, which generates inactive NAD+. When they added this compound, all of NMN's protective effects disappeared - proving that active NAD+ metabolism is essential for the benefits.

What Does This Mean for Humans?

While this research was conducted in rats and lab cultures, the findings have tantalising implications for human health. The brain's energy metabolism and susceptibility to oxidative stress are similar across mammals, suggesting that NMN might offer similar protections in the human brain.

The brain is extraordinarily energy-hungry, consuming about 20% of our body's energy despite making up only 2% of our body weight. As we age, our brain's ability to generate and use energy efficiently declines, making it more vulnerable to stressors like amyloid-beta oligomers.

By boosting NAD+ levels, NMN may help maintain the brain's metabolic resilience, potentially slowing or even preventing the cognitive decline associated with aging and Alzheimer's disease.

A New Direction for Alzheimer's Research

What makes this research particularly exciting is that it represents a fundamentally different approach to tackling Alzheimer's disease. Many failed Alzheimer's treatments have focused solely on clearing amyloid plaques, but this research suggests that supporting the brain's energy metabolism and antioxidant defenses might be just as important.

This aligns with the emerging understanding of Alzheimer's as a complex metabolic disorder, not just a disease of protein accumulation.

Dr. Wang and colleagues concluded their study by suggesting that "NMN may become a promising therapeutic drug for AD." While we shouldn't get ahead of the research, the potential here is genuinely exciting.

What's Next for NMN Research?

This study adds to the growing body of evidence suggesting that NMN supplementation could benefit brain health. But many questions remain:

• What's the optimal dosage for brain protection in humans?
• When should someone start taking NMN for maximum protective effect?
• Could NMN be combined with other treatments for synergistic effects?
• Would oral supplementation (rather than injection) provide similar benefits?

Clinical trials investigating NMN's effects on human cognitive function are still in their early stages. Until we have more human data, we should view NMN as a promising but unproven approach to brain health.

Nevertheless, this research gives us reason for cautious optimism. In a field that has seen so many disappointments, any approach that shows genuine promise is worth close attention.

If the protective effects observed in this study translate to humans, NMN supplementation could potentially become an important part of our strategy for maintaining cognitive health as we age. It's not just about living longer - it's about keeping our minds sharp and our memories intact throughout our extended lifespans.

References

• Wang, X., Hu, X., Yang, Y., Takata, T., & Sakurai, T. (2016). Nicotinamide mononucleotide protects against β-amyloid oligomer-induced cognitive impairment and neuronal death. Brain Research, 1643, 1-9.
• Long, A.N., Owens, K., Schlappal, A.E., Kristian, T., Fishman, P.S., & Schuh, R.A. (2015). Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurology, 15, 19.
• Yao, Z., Yang, W., Gao, Z., & Jia, P. (2017). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neuroscience Letters, 647, 133-140.