For more than 100 years, Alzheimer’s disease has been seen as a one-way road.
Once the disease starts, most doctors and researchers believed it could not be stopped, let alone reversed. But a groundbreaking new study offers hope that this may not always be true.
Researchers from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center have found that restoring the brain’s energy balance may not just slow Alzheimer’s—it could even reverse it.
The study, led by Dr. Kalyani Chaubey from the Pieper Laboratory, looked closely at both human brain tissue and mouse models of Alzheimer’s. They found that a key issue in Alzheimer’s brains is a drop in NAD+—a molecule that helps cells produce and manage energy.
Without enough NAD+, brain cells cannot carry out normal functions and begin to break down. This problem is far more severe in people with Alzheimer’s, and the same pattern appears in mice with Alzheimer’s-like symptoms.
To model the disease, researchers used specially engineered mice with human genetic mutations linked to Alzheimer’s. One group had changes in amyloid proteins, while the other had changes in tau proteins. These changes led to severe brain damage, memory loss, and cognitive decline—similar to what happens in people with Alzheimer’s.
The research team tested two major questions: Could maintaining NAD+ levels prevent Alzheimer’s? And more importantly, could restoring NAD+ levels after the disease had already progressed actually reverse it?
They used a special compound called P7C3-A20, developed in their own lab, to bring NAD+ levels back to normal. In past studies, this compound helped with recovery after traumatic brain injury. In the new study, the results were even more striking.
Not only did the compound prevent disease in early stages—it also reversed Alzheimer’s in mice with advanced disease. Their brains repaired major damage, and memory function returned. In blood tests, biomarkers used to diagnose Alzheimer’s also returned to normal.
Dr. Andrew Pieper, the senior author, called it a powerful discovery. “Restoring the brain’s energy balance achieved recovery in both types of Alzheimer’s mouse models. That gives us real hope,” he said.
The researchers also highlighted why their method is different from over-the-counter NAD+ supplements. Many of those raise NAD+ levels too high, which may cause other health problems like cancer. In contrast, their method gently restores NAD+ to a healthy level without going too far.
While this discovery is still in early stages, the research suggests that under the right conditions, even a damaged brain may have the ability to heal. Dr. Pieper emphasized that this is a message of hope: “The effects of Alzheimer’s may not be permanent.”
Their next steps include further lab studies and, eventually, clinical trials to test the treatment in humans. The technology is already being developed by a company called Glengary Brain Health, co-founded by Dr. Pieper.
In short, this study challenges the idea that Alzheimer’s is always a one-way disease. By focusing on restoring the brain’s natural energy systems, scientists may have found a path toward not just slowing Alzheimer’s—but possibly reversing it.
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The study is published in Cell Reports Medicine.
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