Here’s what we’ll cover in this post:
- What makes this study stand out
- What the study found
- Actionable insights for you
Every few years, Alzheimer’s research produces a headline that creates a media frenzy: “Scientists reverse Alzheimer’s in mice.”
This time, the claim is not coming from a fringe outlet. It’s published in Cell Reports Medicine by a research team led by Andrew Pieper, who used a pharmaceutical compound called P7C3-A20 to boost NAD+ levels. This critical metabolic factor regulates the brain’s ability to produce cellular energy and repair damage.
In two Alzheimer’s mouse models, the authors report something unprecedented: not merely slowing decline, but reversing brain degeneration and restoring healthy cognitive function in mice with dementia. If the researchers stopped there, the results would have still been impressive. But it would be easy to dismiss as a mouse-specific result; human brains are much more complex.
They went one step further. They showed that the same disease patterns they improved in mice also show up in human Alzheimer’s brains. That includes lower NAD+ and shifts in key brain proteins involved in repair, inflammation, and stress response.
Let’s break down what the study actually showed, separate hype from promise, and outline the key takeaways for your brain health strategy.
What drives Alzheimer’s disease, and where does NAD+ fit into the picture?
Alzheimer’s is often described as plaque buildup that disrupts brain cell function, leading to degeneration. So most research and drug development is centered on clearing plaque to improve outcomes.
But plaque is not the whole story. Long before dementia, the aging brain faces other cellular problems: oxidative stress and poor mitochondrial function, less cellular energy, slower repair, inflammation, blood flow issues, and damaged brain barriers. Over time, this leads to widespread degeneration of brain cells and major cognitive decline.
Most people get diagnosed only after symptoms show up. By then, the damage is already advanced. Early symptoms often include trouble learning new information, memory loss, changes in mood and judgment.
So where does NAD+ fit?NAD+ is a helper molecule needed for cellular energy production and to support hundreds of cellular functions involved with stress response and repair. The researchers hypothesized that low NAD+ may be an early trigger of brain degeneration. If that’s true, restoring NAD+ balance might protect brain function. Indeed, previous mouse research shows lower NAD+ levels are associated with Alzheimer’s and cognitive decline.
What makes this study different? Why is it getting so much attention?
This study is drawing attention for a few clear reasons:
- In mouse and human brain samples, NAD+ levels were lower in Alzheimer’s brains and depletion tracked with disease severity.
- Early treatment with an NAD+ booster prevented Alzheimer’s progression.
- Late treatment in mice with severe Alzheimer’s reversed decline and restored cognitive function to that of healthy mice.
- Blood p-tau217 dropped in treated mice. That matters because p-tau217 was recently the first FDA-approved early blood biomarker test for diagnosing Alzheimer’s in humans.
In a field where slowing cognitive decline by 27% is considered a breakthrough, leading to an FDA-approved drug (Lecanemab), a study demonstrating reversal in an Alzheimer’s mouse model with strong overlap to human disease signatures will stand out.
What did the researchers do?
They tested P7C3-A20, a pharmaceutical NAD+ booster that helps cells recycle NAD+ more effectively. It is not like replacing NAD+ directly, but it helps maintain steady levels under stress.
The researchers tested it in two genetic Alzheimer’s mouse models prone to develop sticky brain plaque:
5xFAD: builds up amyloid plaques around brain cells
PS19: builds up tau tangles inside brain cells
Alzheimer’s is not one simple disease. Different people may be affected by different cellular damage patterns. Demonstrating disease reversal in both models adds significant confidence to the findings.
The researchers asked two major questions:
- Can boosting NAD+ early (about 2–6 months in these mice) slow or prevent decline?
- Can boosting NAD+ later (about 6–12 months) restore brain health and function after major damage is already done?
One note for interpretation: most brain tissue tests require sacrificing the mouse. So “reversal” here means that late-stage Alzheimer’s mice looked and functioned more like age-matched healthy controls. Still an unprecedented feat, but not the same as showing reversal in the same brain.
What did the study find?
Across models, treatment with P7C3-A20 was linked to prevention or reversal of Alzheimer’s hallmarks, including:
- Reduced oxidative stress and DNA damage
- Fundamental hallmarks of cellular aging
- Reduced amyloid and tau plaque, the most well-recognized hallmarks of Alzheimer’s
- Less sticky plaque accumulation both inside and between brain cells
- Reduced neuroinflammation
- Inflammation can accelerate brain damage and disrupt brain cell signaling and connectivity
- Reversed blood-brain barrier damage
- The blood-brain barrier is the brain’s security wall. When it becomes leaky, more inflammatory factors and toxins can seep in
- Enhanced markers of neurogenesis in the hippocampus
- Suggesting improved regeneration capacity in the memory center of the brain
- Enhance markers of synaptic plasticity in the hippocampus
- Suggesting improved ability of brain cells to form new connections, supporting learning and memory
- Reduced plasma p-tau217
- This is notable because p-tau217 is used clinically as a blood biomarker test for early Alzheimer’s diagnosis
Most importantly, boosting NAD+ in Alzheimer’s mice fully restored cognitive function in tests of memory and learning, motor coordination, and anxiety-like behaviors. Here’s the simplest way to frame the biology: NAD+ helps brain cells pay for repair when they’re under stress. When NAD+ is low, cellular repair slows and damage piles up. Restoring NAD+ balance may help provide the brain’s repair team with the resources they need to restore order and recover. That is consistent with the multi-system rejuvenation reported here.
Could boosting NAD+ reverse Alzheimer’s disease in humans?
This is the question that naturally enters most of our minds. The study does not prove reversal in humans, but it does add a few reasons for cautious optimism.
First, the human brain tissue data were critical. The study found that human Alzheimer’s brains showed lower NAD+ levels than healthy controls, and disease was worse the lower NAD+ levels were. This is a strong signal that NAD+ depletion may be a causative driver of Alzheimer’s disease and boosting levels may have benefits in humans.Second, they pinpointed a key network of 46 proteins that were altered in both mouse and human Alzheimer’s brains, and restored to normal after treatment with the NAD+ booster. Many of these proteins were important for brain cell metabolism, repair, immune signaling, and the maintenance of healthy signals and connections.
That overlap does not guarantee success in humans. But it suggests the NAD+ booster was acting on a common network of molecular pathways that is present in human disease tissue, not just in a mouse model.
Are the results from the study more hype or hope?
Should we believe headlines that say boosting NAD+ can reverse Alzheimer’s disease?
It’s justified in the narrow sense that treated mice with established Alzheimer’s looked and functioned more like healthy controls than their untreated counterparts.
That is an unprecedented result for Alzheimer’s research. The added human tissue overlap also makes the promise even stronger.
But we need to keep a clear line between mice and humans. Alzheimer’s translation has burned the field many times, and great results in mice don’t always translate to the same results in people.
Here are the biggest caveats:
Humans aren’t mice. Human Alzheimer’s unfolds over decades and is often layered with vascular disease, sleep apnea, insulin resistance, hearing loss, hormone imbalance, and toxin exposure. Mouse models do not capture all of that.
Mouse “cognition” is limited. Improvements in memory, coordination, and anxiety are encouraging, but they do not reflect the complexity of the human mind. Humans rely on language, planning, reasoning, self-reflection, and advanced daily living skills.
While this trial provides promising hints for NAD+’s potential role in human brain health, we need clinical trials that demonstrate meaningful benefits in Alzheimer’s patients.
Still, the study supports an intriguing concept: Toxic plaque buildup may only be a downstream consequence of a much more fundamental cellular problem: energy scarcity and failed resilience. If that’s true, restoring metabolic capacity may reactivate the brain’s ability to repair itself. NAD+ support could become part of future multi-target brain health strategies.And that’s one reason AgelessRx has included NAD+ as part of its multi-intervention strategy for reversing functional brain aging in the globally recognized XPRIZE Healthspan competition.
Actionable insights you can take home today
If your goal is Alzheimer’s prevention, start with what has the strongest human evidence. Large consensus work points to several high-impact levers:
- Reduce risk factors for metabolic and heart disease: obesity, blood pressure, ApoB particles, and insulin resistance all play a role in brain aging.
- Maintain brain fitness and muscle with resistance training and short bouts of high-intensity exercise.
- Address even mild hearing loss with a hearing aid if needed.
- Don’t smoke; keep alcohol modest (ideally ≤1 drink/day) and avoid bingeing.
- Prioritize sleep and treat sleep apnea or heavy snoring.
- Protect against head injury and unnecessary high-impact risk.
- Stay socially engaged and mentally active.
- Manage chronic stress with tools you can sustain (breathwork, mindfulness, journaling).
- Correct common deficiencies linked to brain health: vitamin D, B12, omega-3s (based on labs).
These sound like the boring basics, but research suggests they can cut risk by 40-50%.
Now, where does NAD+ fit into your cognitive health strategy?
Think of NAD+ as neurological capacity or resilience. Lifestyle change addresses systemic risk factors and behaviors that increase damage load. NAD+ boosters may provide precision cellular support to help neurons handle stress and damage more efficiently.
This may also address a real-world puzzle: some people die with extensive brain degeneration but never develop symptoms of Alzheimer’s; researchers call that cognitive resilience. NAD+ boosters may help strengthen cognitive resilience to support longevity.
Which NAD+ booster is best for cognitive health?
Oral NAD+ precursors like NR and NMN may help some people, but results vary due to individual differences in absorption and poor quality control standards for supplements. Further, with oral capsules, it’s hard to know how much reaches the brain.
This is one reason pharmaceutical-grade, clinician-supervised options may be superior when someone is exploring NAD+ support, including: rigorous quality control, more predictable dosing, and medical oversight to help tailor dose and regimen to optimize benefits.AgelessRx’s prescription NAD+ Nasal Spray was developed to enhance cognitive function and brain health by delivering NAD+ closer to the brain. If you’re interested in optimizing your brain health and cognitive function, explore whether NAD+ Nasal Spray is right for you.
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Note: The above statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.