For more than a hundred years, Alzheimer’s disease has been treated as a one-way path. Once it begins, the best we hope for is to slow it down. Recovery was never really part of the conversation. Despite decades of research and enormous investment, no clinical trial has ever set out with the goal of reversing Alzheimer’s and restoring normal brain function.
A new study suggests that this assumption may be wrong.
Researchers from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center have shown that Alzheimer’s disease can be reversed in animal models—even after the disease has reached advanced stages. Their findings, published in Cell Reports Medicine, challenge one of the most deeply rooted beliefs in Alzheimer’s research.
The study focuses on a molecule called NAD+, which plays a central role in how cells produce and manage energy. As we age, NAD+ levels naturally decline throughout the body, including in the brain. When this balance is lost, cells gradually lose their ability to function and survive. The researchers found that this decline is far more severe in the brains of people with Alzheimer’s, as well as in animal models of the disease.
To explore whether restoring this balance could change the course of Alzheimer’s, the team studied two different mouse models. One model reflected amyloid-related disease, while the other focused on tau pathology—two of the earliest and most damaging processes in Alzheimer’s. In both cases, the mice developed brain changes that closely resemble human Alzheimer’s: inflammation, breakdown of the blood-brain barrier, damaged neurons, impaired brain plasticity, oxidative stress, and profound memory loss.
The key question was simple but bold: if the brain’s energy balance is restored after the damage is already done, can the brain recover?
Using a compound called P7C3-A20, developed in the Pieper laboratory, the researchers tested both prevention and late-stage treatment. The results were unexpected and striking. Preserving NAD+ balance prevented Alzheimer’s from developing. Even more surprisingly, restoring NAD+ balance in mice with advanced disease reversed major brain pathology and fully restored cognitive function.
Biological markers told the same story. Levels of phosphorylated tau 217—now an approved blood biomarker for Alzheimer’s in humans—returned to normal, reinforcing the idea that the disease itself had been reversed, not merely slowed.
Dr. Andrew Pieper, senior author of the study, described the results as deeply encouraging. The same recovery was observed in two very different disease models, each driven by different genetic mechanisms. This consistency suggests that restoring the brain’s energy balance may address a core process underlying Alzheimer’s, rather than just one specific pathway.
Importantly, this approach differs from commonly available NAD+ supplements. Over-the-counter precursors can push NAD+ levels too high in animal studies, which may carry serious risks. In contrast, P7C3-A20 helps cells maintain normal NAD+ balance under stress without forcing levels beyond their natural range.
The broader message of the study is difficult to ignore. Alzheimer’s may not be an irreversible condition after all. Under the right conditions, the brain appears capable of repairing itself—even after significant damage has occurred.
This work opens the door to a new way of thinking about Alzheimer’s treatment. Instead of accepting decline as inevitable, future therapies may aim to restore the brain’s ability to function and heal. The research team is now working toward carefully designed human clinical trials to determine whether these results can be replicated in patients.
If these findings translate to humans, they could mark a profound shift—not just in how Alzheimer’s is treated, but in how we understand the brain’s capacity for recovery.