Could Fixing Brain Energy Help Treat Alzheimer’s? Mouse Studies Show Promise
A new study in mice found that balancing cellular energy levels could treat learning and memory problems. This approach could lead to the development of a new Alzheimer’s drug.
Balancing the cellular energy books could provide a new approach to treating Alzheimer’s. As we age, levels of a key molecule that regulates cellular energy, called NAD+, declines.
A few small studies have attempted to test whether over-the-counter NAD+-boosting supplements could treat Alzheimer’s, but the studies are preliminary and their results have been inconclusive. Dr. Andrew A. Pieper, psychiatrist and neuroscientist at Case Western, developed an experimental drug called P7C3-A20 that restores a cell’s ability to regulate its NAD+ levels and was previously tested in animal models of chronic traumatic brain injury.
His latest study published in Cell Reports Medicine found the drug helped restore energy balance and reverse Alzheimer’s-like deficits in different mouse models. “The brain has to use energy to repair itself,” Pieper told Being Patient. Problems regulating these energy levels, he said, “could take the brain to a tipping point where Alzheimer’s disease starts to manifest.”
Pieper emphasized that this is a step toward starting human trials, but it isn’t clear yet whether it will work in humans.
Restoring the energy balance
Pieper wanted to know whether restoring energy balance could both prevent Alzheimer’s and treat its symptoms.
The team used what’s called a 5xFAD mouse model because it’s genetically modified with five genetic mutations that affect beta-amyloid processing, which causes familial Alzheimer’s in humans. These mice develop learning and memory problems at six months, and the researchers found their NAD+ levels dropped as well.
Treating them with P7C3-A20 early helped them maintain a healthy energy balance and prevented the development of Alzheimer’s-like deficits, though it didn’t clear out the beta-amyloid. When researchers waited until the mice developed memory and learning problems, fixing the energy balance with the drug also treated the symptoms.
Pieper’s team also found that the drug reduced cellular damage and increased the number of new brain cells formed.
To make sure the results were robust across different models of the disease, they tested the drug again in the PS19 mouse model, which develops tau tangles, another hallmark of Alzheimer’s. Again, they found that their treatment could restore the ability to regulate energy levels and reverse the learning and memory symptoms.
P7C3-A20 vs NAD+ supplements
While P7C3-A20 and NAD-boosting supplements affect cellular energy levels, they do so differently.
P7C3-A20 targets cellular machinery to regulate NAD+ levels. When the researchers gave the drug to healthy mice, it didn’t change their NAD+ levels since they were ideal. By contrast, NAD+-boosting supplements simply raise the levels of NAD+ even if they’re already high.
“There have been many papers already published to demonstrate that boosting NAD+ ameliorates the pathology of Alzheimer’s disease in mice,” Dr. Shin-ichiro Imai, a professor at Washington University in St. Louis who studies NAD+ and energy balance, and who wasn’t involved in the study, told Being Patient.
Whether the benefits of P7C3-A20 surpass other NAD+ supplements is unclear based on this study, he said, and requires further research.
Should you take NAD+ energy boosting supplements?
The effects of supplements and drugs that work well in mouse models of disease often don’t translate into humans. But NAD-boosting supplements in the form of nicotinamide riboside (NR) and NMN (nicotinamide mononucleotide) are widely available.
“There are so many hundreds and hundreds of products available, and unfortunately, the quality of products is really highly variable,” Imai said. Like many other supplements, the dose on the label doesn’t match the ingredients, and in some cases the advertised ingredient isn’t even in the supplement. Some have independent third-party certification like NSF, which verifies the ingredients and dosage.
It is also unclear whether NAD+-boosting supplements provide a clinical benefit. In his work, Imai has found variability in how individuals respond to these supplements, suggesting that they won’t work for everyone.
As of January 2026, there were three active clinical trials of Alzheimer’s testing various NAD+-boosting supplements.
Some researchers have cautioned that these over-the-counter supplements may cause problems if levels are increased too high. Studies in mice with cancer suggest these supplements might fuel the disease but don’t seem to cause cancer in healthy mice. While generally safe, Imai cautioned that there may be risk for cancer survivors.
“Some studies in the published literature have shown that there are risks associated with elevating NAD+ levels too high, whereas others have not,” Pieper said. “Anyone considering taking a supplement should talk to their physician about whether or not it’s a good idea with respect to their particular health conditions.”
What’s next for P7C3-A20?
One thing that isn’t clear yet is whether the reversal is permanent. In ongoing studies, Pieper’s team is testing whether the benefits of the drug persist even after they stop administering it to the mice. That could answer whether P7C3-A20 provides a permanent fix.
P7C3-A20 is being further developed by Glengarry Brain Health, a Cleveland-based biotechnology company founded by Pieper.
Since drugs that are efficiently absorbed and reach the brain in mice don’t always do the same in humans, the team is working on a version of it that might work better in humans. “We’ve made really good progress on that so far but aren’t there yet,” Pieper said. “We hope that within a couple of years we can start Phase 1 safety trials.”
